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1.
Biomed Eng Online ; 23(1): 25, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38419078

RESUMO

BACKGROUND: The accurate detection of eyelid tumors is essential for effective treatment, but it can be challenging due to small and unevenly distributed lesions surrounded by irrelevant noise. Moreover, early symptoms of eyelid tumors are atypical, and some categories of eyelid tumors exhibit similar color and texture features, making it difficult to distinguish between benign and malignant eyelid tumors, particularly for ophthalmologists with limited clinical experience. METHODS: We propose a hybrid model, HM_ADET, for automatic detection of eyelid tumors, including YOLOv7_CNFG to locate eyelid tumors and vision transformer (ViT) to classify benign and malignant eyelid tumors. First, the ConvNeXt module with an inverted bottleneck layer in the backbone of YOLOv7_CNFG is employed to prevent information loss of small eyelid tumors. Then, the flexible rectified linear unit (FReLU) is applied to capture multi-scale features such as texture, edge, and shape, thereby improving the localization accuracy of eyelid tumors. In addition, considering the geometric center and area difference between the predicted box (PB) and the ground truth box (GT), the GIoU_loss was utilized to handle cases of eyelid tumors with varying shapes and irregular boundaries. Finally, the multi-head attention (MHA) module is applied in ViT to extract discriminative features of eyelid tumors for benign and malignant classification. RESULTS: Experimental results demonstrate that the HM_ADET model achieves excellent performance in the detection of eyelid tumors. In specific, YOLOv7_CNFG outperforms YOLOv7, with AP increasing from 0.763 to 0.893 on the internal test set and from 0.647 to 0.765 on the external test set. ViT achieves AUCs of 0.945 (95% CI 0.894-0.981) and 0.915 (95% CI 0.860-0.955) for the classification of benign and malignant tumors on the internal and external test sets, respectively. CONCLUSIONS: Our study provides a promising strategy for the automatic diagnosis of eyelid tumors, which could potentially improve patient outcomes and reduce healthcare costs.


Assuntos
Neoplasias Palpebrais , Humanos , Neoplasias Palpebrais/diagnóstico , Área Sob a Curva , Custos de Cuidados de Saúde
2.
Biochem Biophys Res Commun ; 662: 104-113, 2023 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-37104880

RESUMO

Acute liver failure (ALF) is a clinical syndrome characterized by the accelerated development of hepatocyte necrosis and significant mortality. Given that liver transplantation is now the only curative treatment available for ALF, there is an urgent need to explore innovative therapies. Mesenchymal stem cells (MSCs) have been applied in preclinical studies for ALF. It had been demonstrated that human embryonic stem cell-derived immunity-and-matrix regulatory cells (IMRCs) met the properties of MSCs and had been employed in a wide range of conditions. In this study, we conducted a preclinical evaluation of IMRCs in the treatment of ALF and investigated the mechanism involved. ALF was induced in C57BL/6 mice via intraperitoneal administration of 50% CCl4 (6 mL/kg) mixed with corn oil, followed by intravenous injection of IMRCs (3 × 106 cells/each). IMRCs improved histopathological changes in the liver and reduced alanine transaminase (ALT) or aspartate transaminase (AST) levels in serum. IMRCs also promoted cell renewal in the liver and protected it from CCl4 damage. Furthermore, our data indicated that IMRCs protected against CCl4-induced ALF by regulating the IGFBP2-mTOR-PTEN signaling pathway, which is associated with the repopulation of intrahepatic cells. Overall, IMRCs offered protection against CCl4-induced ALF and were capable of preventing apoptosis and necrosis in hepatocytes, which provided a new perspective for treating and improving the prognosis of ALF.


Assuntos
Células-Tronco Embrionárias Humanas , Falência Hepática Aguda , Transplante de Células-Tronco Mesenquimais , Camundongos , Animais , Humanos , Camundongos Endogâmicos C57BL , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/terapia , Falência Hepática Aguda/patologia , Fígado/metabolismo , Hepatócitos/patologia , Necrose/patologia
3.
Org Biomol Chem ; 20(4): 870-876, 2022 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-35006233

RESUMO

Seventeen C20-O-alkyl/benzyl oxime derivatives were synthesized by a concise and effective method. Most of these derivatives showed tens to several hundred nanomolar IC50 values against HT-29 colorectal, HGC-27 gastric and MDA-MB-231 breast cancer cells, whose antiproliferative activity is 15-240 fold better than that of salinomycin. The C20-oxime etherified derivatives can coordinate potassium ions, and further adjust the cytosolic Ca2+ concentrations in HT-29 cells. The significant improvement of the potency should be attributed to the better ion binding and transport ability of the modified derivatives. In addition, the C20-O-alkyl/benzyl oxime derivatives showed much better selectivity indexes (SI) than salinomycin, indicating that they present lower neurotoxic risk.


Assuntos
Antineoplásicos/farmacologia , Oximas/farmacologia , Piranos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Modelos Moleculares , Conformação Molecular , Oximas/síntese química , Oximas/química , Piranos/síntese química , Piranos/química
4.
Phys Chem Chem Phys ; 24(2): 1091-1098, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34927655

RESUMO

Two-dimensional (2D) materials with intrinsic ferromagnetism and piezoelectricity have received growing attention due to their potential applications in nanoscale spintronic devices. However, their applications are highly limited by the low Curie temperatures (TC) and small piezoelectric coefficients. Here, using first-principles calculations, we have successfully predicted that BiCrX3 (X = S, Se, and Te) monolayers simultaneously possess ferromagnetism and piezoelectricity by replacing one layer of Bi atoms with Cr atoms in Bi2X3 monolayers. Our results demonstrate that BiCrX3 monolayers are not only intrinsic ferromagnetic semiconductors with indirect band gaps, adequate TC values of higher than 300 K, and significant out-of-plane magnetic anisotropic energies, but also exhibit appreciable in-plane and out-of-plane piezoelectricity. In particular, the in-plane piezoelectric coefficients of BiCrX3 monolayers with ABCAB configuration are up to 15.16 pm V-1, which is higher than those of traditional three-dimensional piezoelectric materials such as α-quartz. The coexistence of ferromagnetism and piezoelectricity in BiCrX3 monolayers gives them promising applications in spintronics and nano-sized sensors.

5.
Phys Chem Chem Phys ; 24(34): 20530-20537, 2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-35996999

RESUMO

Due to their potential application in spintronic devices, two-dimensional (2D) ferromagnetic materials are highly desired. We used first-principles calculations and Monte Carlo simulations to investigate the electronic structure and magnetic characteristics of the MnOCl2 monolayers. We discovered two stable monolayer structures, Pmna-MnOCl2 and Pmmn-MnOCl2. Our findings show that the Pmna-MnOCl2 monolayer is an intrinsic ferromagnetic semiconductor with an indirect band gap of 0.152 eV and a Curie temperature (TC) of 202 K, while the Pmmn-MnOCl2 monolayer is an intrinsic ferromagnetic Dirac semimetal with a high TC (910 K) and triaxial magnetic anisotropy. We also show that a Pmmn-MnOCl2 monolayer with a nontrivial band gap of 6.2 meV can achieve the quantum anomalous Hall effect (QAHE) with Chern number C = 1. Additionally, the existence of a gapless edge state can be flexibly regulated by choosing the terminal edges. Our studies reveal that the Pmmn-MnOCl2 monolayer can serve as a candidate material to achieve high-temperature QAHE.

6.
BMC Surg ; 22(1): 25, 2022 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-35081938

RESUMO

BACKGROUND: Laparoscopic Ladd's procedure for malrotation in children is still a controversial approach. Although some retrospective studies have compared the outcomes of the two types of procedure with inconsistency outcomes. Currently, there are few large-scale studies on laparoscopic treatment in malrotation with neonates and infants. We did a study based on propensity score matching to compare the effects of the two kinds of approach in neonates and infants. To investigate the therapeutic effect of laparoscopy and open Ladd's procedure by the propensity score-matching (PSM) to enhance the validity of the comparison. METHODS: A total series of 143 cases of intestinal malrotation without intestinal necrosis was included in the study during the 8 years from January 2012 to January 2020, including 68 cases of open Ladd's procedure and 75 cases of laparoscopic Ladd's procedure including five cases of transfer laparotomy. By a propensity score 1:1 matching, 62 patients were stratified for each group. RESULTS AND CONCLUSION: There was no significant difference in volvulus degree, weight and gender between the two groups (p > 0.05). Laparoscopic surgery took more time than open surgery (105.9 min vs 70.6 min, p < 0.05), but it had less hospital stay (12.4 days vs 14.6 days, p < 0.05) or less incision infection (0 vs 6, p < 0.05). There was no significant difference between the two groups at the time of first defecation, blood loss, time of full feeding and reoperation (p > 0.05). The cosmetic effect of laparoscopic surgery is better than that of open surgery. Laparoscopic Ladd's procedure is a safe approach. It can reduce the length of hospital stay and incision infection, but the operation time was extended, the other complications are similar compared with open procedure for intestinal malrotation in neonates and infants.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório , Volvo Intestinal , Laparoscopia , Criança , Humanos , Lactente , Recém-Nascido , Volvo Intestinal/cirurgia , Pontuação de Propensão , Estudos Retrospectivos
7.
J Minim Access Surg ; 18(3): 472-474, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35708392

RESUMO

There are fewer reports of thoracoscopic surgical resection of mediastinal cysts in neonates. The aim of this article is to report on the feasibility of thoracoscopic resection of a large mediastinal cyst and the management of chylothorax after surgery in neonates.

8.
J Minim Access Surg ; 17(4): 486-489, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33885012

RESUMO

OBJECTIVE: The objective of the study is to explore a less invasive laparoscopic pyloromyotomy for treating infantile hypertrophic pyloric stenosis. PATIENTS AND METHODS: A series of 154 cases from January 2014 to January 2020 were retrospectively analysed. Seventy patients were treated with the method of transumbilical single-site laparoscopic pyloromyotomy (SSLP), and 84 patients were treated with two-site laparoscopic pyloromyotomy. There was no difference in the body weight, sex ratio or age between the two groups. The operation time, blood loss, post-operative feeding time and complications between the two groups were compared. RESULTS: The novel single-site method had better cosmetic effect than the two-site approach. There was no difference in the operation time, blood loss, post-operative feeding time or complications between the two groups. CONCLUSION: The novel SSLP method requires only two incisions through the umbilicus to complete the procedure, with barely visible scars and similar surgical complications to that of the two-site approach; thus, the novel method is worth promoting.

9.
Sensors (Basel) ; 20(15)2020 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-32708002

RESUMO

The original pattern recognition and classification of crop diseases needs to collect a large amount of data in the field and send them next to a computer server through the network for recognition and classification. This method usually takes a long time, is expensive, and is difficult to carry out for timely monitoring of crop diseases, causing delays to diagnosis and treatment. With the emergence of edge computing, one can attempt to deploy the pattern recognition algorithm to the farmland environment and monitor the growth of crops promptly. However, due to the limited resources of the edge device, the original deep recognition model is challenging to apply. Due to this, in this article, a recognition model based on a depthwise separable convolutional neural network (DSCNN) is proposed, which operation particularities include a significant reduction in the number of parameters and the amount of computation, making the proposed design well suited for the edge. To show its effectiveness, simulation results are compared with the main convolution neural network (CNN) models LeNet and Visual Geometry Group Network (VGGNet) and show that, based on high recognition accuracy, the recognition time of the proposed model is reduced by 80.9% and 94.4%, respectively. Given its fast recognition speed and high recognition accuracy, the model is suitable for the real-time monitoring and recognition of crop diseases by provisioning remote embedded equipment and deploying the proposed model using edge computing.


Assuntos
Algoritmos , Redes Neurais de Computação , Simulação por Computador
10.
Bioorg Med Chem Lett ; 29(7): 870-872, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30772099

RESUMO

Aberrant Wnt signaling has been implicated in a variety of disease. Inhibition of the Wnt pathway is an attractive approach for developing new therapeutics for the treatment of various types of fibrosis and cancers. We have discovered the phthalimide-phenylpyridine conjugate as a novel hit compound for the Wnt pathway inhibitors from cellular screening. The structure-activity relationship of these compounds suggested both of the substituent group on the phthalimide fragment and the structure of the linker were critical to the inhibitory activity. The most potent compound was about 10-folds more potent than the hit compound, with IC50 value of 0.28 ±â€¯0.01 µM.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Pirazinas/farmacologia , Piridinas/farmacologia , Pirimidinonas/farmacologia , Via de Sinalização Wnt/efeitos dos fármacos , Compostos Bicíclicos Heterocíclicos com Pontes/química , Estrutura Molecular , Pirazinas/química , Piridinas/química , Pirimidinonas/química , Transdução de Sinais/efeitos dos fármacos , Relação Estrutura-Atividade
11.
Reprod Biol Endocrinol ; 16(1): 61, 2018 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-29935533

RESUMO

BACKGROUND: This population-based study was designed to investigate whether consumption of sugar-sweetened beverages (SSB) is associated with lower serum total testosterone concentration in men 20-39 years old. METHODS: All data for this study were retrieved from the National Health and Nutrition Examination Survey (NHANES) 2011-2012. The primary outcome was serum testosterone concentration, and main independent variable was SSB intake. Other variables included age, race/ethnicity, poverty/income ratio, body mass index (BMI), serum cotinine, heavy drinking, and physical activity. RESULTS: Among all subjects (N = 545), 486 (90.4%) had normal testosterone levels (defined as ≥231 ng/dL) and 59 (9.6%) had low testosterone levels (defined as < 231 ng/dL). Multivariate logistic regression revealed the odds of low testosterone was significantly greater with increasing SSB consumption (Q4 [≥442 kcal/day] vs. Q1 [≤137 kcal/day]), adjusted odds ratio [aOR] = 2.29, p = 0.041]. After adjusting for possible confounding variables, BMI was an independent risk factor for low testosterone level; subjects with BMI ≥ 25 kg/m2 had a higher risk of having a low testosterone level than those with BMI < 25 kg/m2 (aOR = 3.68, p = 0.044). CONCLUSION: SSB consumption is significantly associated with low serum testosterone in men 20-39 years old in the United States.


Assuntos
Bebidas , Sacarose Alimentar/administração & dosagem , Sacarose Alimentar/metabolismo , Edulcorantes/administração & dosagem , Testosterona/sangue , Adulto , Bebidas/efeitos adversos , Biomarcadores/sangue , Sacarose Alimentar/efeitos adversos , Humanos , Masculino , Inquéritos Nutricionais/tendências , Açúcares/administração & dosagem , Açúcares/efeitos adversos , Edulcorantes/efeitos adversos , Estados Unidos/epidemiologia , Adulto Jovem
13.
Stem Cells ; 34(5): 1310-20, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26930448

RESUMO

Retaining muscle stem satellite cell (SC) quiescence is important for the maintenance of stem cell population and tissue regeneration. Accumulating evidence supports the model where key extracellular signals play crucial roles in maintaining SC quiescence or activation, however, the intracellular mechanisms that mediate niche signals to control SC behavior are not fully understood. Here, we reported that KLF7 functioned as a key mediator involved in low-level TGF-ß signaling and canonical Notch signaling-induced SC quiescence and myoblast arrest. The data obtained showed that KLF7 was upregulated in quiescent SCs and nonproliferating myoblasts. Silence of KLF7 promoted SCs activation and myoblasts proliferation, but overexpression of KLF7 induced myogenic cell arrest. Notably, the expression of KLF7 was regulated by TGF-ß and Notch3 signaling. Knockdown of KLF7 diminished low-level TGF-ß and canonical Notch signaling-induced SC quiescence. Investigation into the mechanism revealed that KLF7 regulation of SC function was dependent on p21 and acetylation of Lys227 and/or 231 in the DNA binding domain of KLF7. Our study provides new insights into the regulatory network of muscle stem cell quiescence. Stem Cells 2016;34:1310-1320.


Assuntos
Ciclo Celular , Espaço Extracelular/metabolismo , Fatores de Transcrição Kruppel-Like/metabolismo , Células Satélites de Músculo Esquelético/citologia , Células Satélites de Músculo Esquelético/metabolismo , Transdução de Sinais , Acetilação , Sequência de Aminoácidos , Animais , Pontos de Checagem do Ciclo Celular , Diferenciação Celular/genética , Linhagem Celular , Proliferação de Células , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Humanos , Fatores de Transcrição Kruppel-Like/química , Camundongos , Desenvolvimento Muscular , Receptores Notch/metabolismo , Ativação Transcricional/genética , Fator de Crescimento Transformador beta/metabolismo , Regulação para Cima
14.
Bioorg Med Chem Lett ; 27(7): 1624-1626, 2017 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-28262526

RESUMO

Several salinomycin-hydroxamic acid conjugates were designed and synthesized. Most conjugates showed better antiproliferative activities than salinomycin in HT-29 colon cancer, HGC-27 gastric cancer, and especially in MDA-MB-231 triple-negative human breast cancer cells. These conjugates are stable in cell culture media, and they showed much better biological activities than the 1:1 physical mixture with hydroxamic acids and salinomycin. The better membrane permeability and hydrolysis rate of the conjugates may lead to the activity improvements.


Assuntos
Antineoplásicos/farmacologia , Ácidos Hidroxâmicos/farmacologia , Piranos/farmacologia , Antineoplásicos/síntese química , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Estabilidade de Medicamentos , Humanos , Ácidos Hidroxâmicos/síntese química , Piranos/síntese química
15.
Asian-Australas J Anim Sci ; 30(6): 857-864, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27809464

RESUMO

OBJECTIVE: The purpose of this study was to investigate the influence of AMP-activated protein kinase (AMPK) activation on protein acetylation and glycolysis in postmortem muscle to better understand the mechanism by which AMPK regulates postmortem glycolysis and meat quality. METHODS: A total of 32 mice were randomly assigned to four groups and intraperitoneally injected with 5-Aminoimidazole-4-carboxamide1-ß-D-ribofuranoside (AICAR, a specific activator of AMPK), AICAR and histone acetyltransferase inhibitor II, or AICAR, Trichostatin A (TSA, an inhibitor of histone deacetylase I and II) and Nicotinamide (NAM, an inhibitor of the Sirt family deacetylases). After mice were euthanized, the Longissimus dorsi muscle was collected at 0 h, 45 min, and 24 h postmortem. AMPK activity, protein acetylation and glycolysis in postmortem muscle were measured. RESULTS: Activation of AMPK by AICAR significantly increased glycolysis in postmortem muscle. At the same time, it increased the total acetylated proteins in muscle 45 min postmortem. Inhibition of protein acetylation by histone acetyltransferase inhibitors reduced AMPK activation induced increase in the total acetylated proteins and glycolytic rate in muscle early postmortem, while histone deacetylase inhibitors further promoted protein acetylation and glycolysis. Several bands of proteins were detected to be differentially acetylated in muscle with different glycolytic rates. CONCLUSION: Protein acetylation plays an important regulatory role in postmortem glycolysis. As AMPK mediates the effects of pre-slaughter stress on postmortem glycolysis, protein acetylation is likely a mechanism by which antemortem stress influenced postmortem metabolism and meat quality though the exact mechanism is to be elucidated.

16.
Nanotechnology ; 27(1): 015703, 2016 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-26594911

RESUMO

In this work, self-assembled ferroelectric BiFeO3 (BFO) and Pb(Zr,Ti)O3 (PZT) nanocapacitors were fabricated by a one-step pulsed-laser deposition process. Each individual nanocapacitor consists of a SrRuO3 or LaSrMnO3 bottom electrode layer, an epitaxial ferroelectric middle layer and a self-assembled nanoisland of conductive Bi2O3 or PbO2 as the top nanoelectrode. The nanoelectrodes have a lateral size of 10-100 nm depending on various deposition equivalent thickness. The as-fabricated nanocapacitors exhibit unique so-called anti-domain structures, with opposite polarization orientation to that of the naked ferroelectric films, which can be understood by the different interface built-in-voltages between their neighboring layers. They also show apparent reduced coercive fields and enhanced piezoelectricity compared to the naked films, as revealed by the switching spectroscopy piezoresponse force microscopy (SSPFM) and band-excitation mapping. Besides that, individual addressable polarization writing and erasing properties were also observed in these nanocapacitors and the written domain can maintain stability up to 12 h, which is promising for data storage devices.

17.
Nanotechnology ; 27(48): 485302, 2016 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-27819797

RESUMO

Efficient and cost-competitive fabrication of high-quality ferroelectric and multiferroic nanostructures is of general interest. In this work, a top-down nano-patterning technique is developed by the Ar+ ion beam etching in combination with the sacrificed ultrathin anodic alumina (AAO) mask. This technique is demonstrated by preparation of the epitaxial BiFeO3 (BFO) nanostructures of various geometries, including nanodot and anti-nanodot arrays. The lateral dot size is as small as ∼60 nm and an ultrahigh dot density of ∼60 Gbit/inch2 is achieved. It is revealed that the etching process involves sequential shape evolution of both the AAO mask and the underlying BFO film, resulting in the nanodots and anti-nanodots arrays of various geometries. The as-etched BFO nanodots array exhibits well-established ferroelectric domain structures and reversible polarization switching, as examined by piezoresponse force microscopy (PFM). It is suggested that this technique is extendable to fabrication of a wide range of functional oxide nanostructures for potential nanoelectronic applications.

18.
J Cell Physiol ; 230(5): 1003-12, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25200835

RESUMO

MicroRNAs (miRNAs) are a group of small noncoding RNAs that regulate the stability or translation of cognate mRNAs at the post-transcriptional level. Accumulating evidence indicates that miRNAs play important roles in many aspects of muscle function, including muscle growth and development, regeneration, contractility, and muscle fiber type plasticity. In the current study, we examined the function of miR-151-3p in myoblast proliferation and differentiation. Results show that overexpression of miR-151-3p not only upregulates myoblast proliferation, but also decreases slow muscle gene expression (such as MHC-ß/slow and slow muscle troponin I) in both C2C12 myotubes and in primary cultures. Alternatively, inhibition of miR-151-3p by antisense RNA was found to upregulate MHC-ß/slow expression, indicating that miR-151-3p plays a role in muscle fiber type determination. Further investigation into the underlying mechanisms revealed for the first time that miR-151-3p directly targets ATP2a2, a gene encoding for a slow skeletal and cardiac muscle specific Ca(2+) ATPase, SERCA2 thus downregulating slow muscle gene expression. Mechanisms by which the alteration in SERCA2 expression induces changes in other slow muscle gene expression levels needs to be defined in future research.


Assuntos
Regulação da Expressão Gênica , MicroRNAs/metabolismo , Células Musculares/metabolismo , Fibras Musculares de Contração Lenta/citologia , Fibras Musculares de Contração Lenta/metabolismo , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Adenoviridae/metabolismo , Animais , Diferenciação Celular/genética , Linhagem Celular , Proliferação de Células , Regulação para Baixo/genética , Técnicas de Silenciamento de Genes , Humanos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Desenvolvimento Muscular , Fibras Musculares Esqueléticas/metabolismo , Mioblastos , Cadeias Pesadas de Miosina/metabolismo , Especificidade de Órgãos/genética , RNA Interferente Pequeno/metabolismo
19.
Biochem Biophys Res Commun ; 458(3): 449-455, 2015 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-25637528

RESUMO

Dysregulation of lipid metabolism has been believed to be central in the development of skeletal muscle insulin resistance. Since first being described in 1989, the role of AMPK in energy metabolism, especially its role in lipid metabolism in skeletal muscle has been well studied. However, some recent literature report that fatty acid oxidation in skeletal muscle is not directly associated with AMPK activation and ACC phosphorylation. To further understand the role of AMPK in lipid metabolism and the development of induced obesity and insulin resistance, muscle specific AMPKα2 knockout mice (mAMPKα2-KO) was employed in this study. The results showed that AMPKα2 ablation in muscle did not exacerbate high fat diet induce obesity in mice. On the contrary, it improved animal glucose tolerance and insulin sensitivity, with reduced triglyceride content in skeletal muscle and fat mass in various adipose tissues, when mice were fed high fat diet for 14 weeks. Gene expression analysis revealed that AMPKα2 knockout up-regulated the expression of genes related to lipid catabolism and down-regulated that of genes related to triglyceride synthesis. More importantly, ablation of AMPKα2 altered the expression of several myokines related to adipogenesis and muscle regeneration. Our data suggest that defect in AMPKα2 signaling does not necessarily lead to the development of muscle insulin resistance and obesity. AMPKα2 may regulate whole body lipid metabolism by regulating myokine secretion.


Assuntos
Proteínas Quinases Ativadas por AMP/genética , Dieta Hiperlipídica/efeitos adversos , Metabolismo dos Lipídeos , Músculos/enzimologia , Obesidade/enzimologia , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Deleção de Genes , Regulação da Expressão Gênica , Resistência à Insulina , Camundongos , Camundongos Knockout , Músculos/metabolismo , Obesidade/genética , Obesidade/metabolismo
20.
J Org Chem ; 80(19): 9392-400, 2015 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-26339716

RESUMO

A general and efficient phosphorous acid-catalyzed cyclocondensation of ß-ketoesters with o-aminobenzamides via selective C-C bond cleavage leading to quinazolinones is developed. This reaction proceeds smoothly under metal- and oxidant-free conditions, giving both 2-alkyl- and 2-aryl-substituted quinazolinones in excellent yields. This strategy can also be applied to the synthesis of other N-heterocycles, such as benzimidazoles and benzothiazoles.

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