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1.
Expert Rev Clin Pharmacol ; 15(7): 799-803, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35848442

RESUMO

INTRODUCTION: Diabetic patients are prone to hypoglycemia when treated with insulin. Dasiglucagon is a water-soluble and ready-to-use glucagon analog developed for treating hypoglycemia in patients with diabetes. AREAS COVERED: A comprehensive literature search was conducted in PubMed. Key search terms included dasiglucagon and hypoglycemia. The pharmacological characteristics, clinical evidence, and place in therapy of dasiglucagon were reviewed. EXPERT OPINION: Dasiglucagon is a glucagon analog that is stable in water-soluble formulation. It can increase plasma glucose in a dose-dependent manner. Clinical studies have shown that dasiglucagon rapidly and effectively improved insulin-induced hypoglycemia in patients with diabetes. Dasiglucagon was well tolerated and the common adverse events included nausea and vomiting.


Assuntos
Diabetes Mellitus Tipo 1 , Hipoglicemia , Glicemia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Glucagon/efeitos adversos , Glucagon/análogos & derivados , Humanos , Hipoglicemia/induzido quimicamente , Insulina , Água/efeitos adversos
3.
Sci Rep ; 11(1): 7291, 2021 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-33790380

RESUMO

The study of cellular complexity in the nervous system based on anatomy has shown more practical and objective advantages in morphology than other perspectives on molecular, physiological, and evolutionary aspects. However, morphology-based neuron type classification in the whole rat brain is challenging, given the significant number of neuron types, limited reconstructed neuron samples, and diverse data formats. Here, we report that different types of deep neural network modules may well process different kinds of features and that the integration of these submodules will show power on the representation and classification of neuron types. For SWC-format data, which are compressed but unstructured, we construct a tree-based recurrent neural network (Tree-RNN) module. For 2D or 3D slice-format data, which are structured but with large volumes of pixels, we construct a convolutional neural network (CNN) module. We also generate a virtually simulated dataset with two classes, reconstruct a CASIA rat-neuron dataset with 2.6 million neurons without labels, and select the NeuroMorpho-rat dataset with 35,000 neurons containing hierarchical labels. In the twelve-class classification task, the proposed model achieves state-of-the-art performance compared with other models, e.g., the CNN, RNN, and support vector machine based on hand-designed features.


Assuntos
Encéfalo/fisiologia , Modelos Neurológicos , Redes Neurais de Computação , Neurônios/classificação , Animais , Encéfalo/citologia , Aprendizado de Máquina , Neurônios/fisiologia , Ratos
4.
Mol Med Rep ; 20(2): 1017-1024, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31173182

RESUMO

Puerarin is the major bioactive ingredient isolated from the dry root of Pueraria lobata, a plant used in traditional Chinese medicine. Puerarin has been used to treat diabetes and cataracts in China; however, its underlying mechanism of action remains unclear. The aim of the present study was to investigate the effectiveness and mechanism of puerarin in preventing cataracts in diabetic rats. Diabetes was induced by streptozocin (STZ) administration and rats were intraperitoneally injected with puerarin (25, 50 and 100 mg/kg). Blood glucose levels and cataract development were examined in the different experimental groups. In addition, the expression levels of markers associated with oxidative stress, including nuclear factor erythroid 2 like 2 (Nrf2) and heme oxygenase­1 (HO­1), were analyzed. The present results suggested that treatment with puerarin at 25, 50 and 100 mg/kg significantly reduced blood glucose levels and the incidence of cataract in STZ­induced diabetic rats. Additionally, puerarin treatment reduced oxidative stress, restoring the levels of malondialdehyde and glutathione, and the activity of glutathione peroxidase. Furthermore, puerarin administration decreased the expression levels of retinal vascular endothelial growth factor and interleukin­1ß and increased the mRNA expression levels of Nrf2 and HO­1, thus inhibiting oxidative stress. The present findings suggested that puerarin had hypoglycemic effects and that it prevented cataract development and progression in diabetic rats by reducing oxidative stress through the Nrf2/HO­1 signaling pathway.


Assuntos
Catarata/prevenção & controle , Diabetes Mellitus Experimental/tratamento farmacológico , Heme Oxigenase (Desciclizante)/genética , Hipoglicemiantes/farmacologia , Isoflavonas/farmacologia , Fator 2 Relacionado a NF-E2/genética , Pueraria/química , Animais , Glicemia/metabolismo , Catarata/induzido quimicamente , Catarata/genética , Catarata/patologia , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patologia , Medicamentos de Ervas Chinesas/química , Regulação da Expressão Gênica , Glutationa/agonistas , Glutationa/metabolismo , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Heme Oxigenase (Desciclizante)/metabolismo , Hipoglicemiantes/isolamento & purificação , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Isoflavonas/isolamento & purificação , Masculino , Malondialdeído/antagonistas & inibidores , Malondialdeído/metabolismo , Fator 2 Relacionado a NF-E2/agonistas , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Ratos , Ratos Wistar , Transdução de Sinais , Estreptozocina , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
5.
Exp Mol Pathol ; 108: 17-23, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30853612

RESUMO

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief. The journal was initially contacted by the corresponding author to report that the article was submitted without the consent of an author. Given the comments of Dr Elisabeth Bik regarding this article "… the Western blot bands in all 400+ papers are all very regularly spaced and have a smooth appearance in the shape of a dumbbell or tadpole, without any of the usual smudges or stains. All bands are placed on similar looking backgrounds, suggesting they were copy/pasted from other sources, or computer generated ", the journal requested the authors to provide the raw data. However, the authors were not able to fulfil this request and therefore the Editor-in-Chief decided to retract the article.


Assuntos
Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Ginsenosídeos/farmacologia , MicroRNAs/genética , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Retinoblastoma/genética , Retinoblastoma/metabolismo , Retinoblastoma/patologia , Serina-Treonina Quinases TOR/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Regulação para Cima/efeitos dos fármacos
6.
J Cell Physiol ; 234(9): 15420-15428, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30701534

RESUMO

Tanshinone IIA is a lipophilic diterpene extracted from the Salvia miltiorrhiza bunge, possessing antiapoptotic and antioxidant activities. The purpose of this study was to explore the effects of Tanshinone IIA on age-related nuclear cataract. Human lens epithelial cell line SRA01/04 was subjected to H 2 O 2 to mimic a cell model of cataract. Cell Counting Kit-8 assay, flow cytometer, and reactive oxygen species (ROS) detection were performed to evaluate the effect of Tanshinone IIA pretreatment on SRA01/04 cells injured by H 2 O 2 . Besides, the real-time quantitative polymerase chain reaction was used to assess the expression of long noncoding RNA (lncRNA) antisense noncoding RNA in the INK4 locus (ANRIL). Western blot analysis was performed to detect the expression of core proteins involved in cell survival and nuclear factor-κB (NF-κB) pathway. H 2 O 2 significantly decreased SRA01/04 cells viability, whereas increased apoptosis and ROS generation. This phenomenon was coupled with the upregulated p53, p21, Bax, cleaved caspase-3, and the downregulated cyclinD1, CDK4, and Bcl-2. Tanshinone IIA pretreatment protected SRA01/04 cells against H 2 O 2 -induced injury. In the meantime, the expression of lncRNA ANRIL was upregulated by Tanshinone IIA. And, the protective effects of Tanshinone IIA on H 2 O 2 -stimulated SRA01/04 cells were abolished when lncRNA ANRIL was silenced. Moreover, the elevated expression of lncRNA ANRIL induced by Tanshinone IIA was abolished by BAY 11-7082 (an inhibitor of NF-κB). To conclude, Tanshinone IIA protects SRA01/04 cells from apoptosis triggered by H 2 O 2 . Tanshinone IIA confers its protective effects possibly via modulation of NF-κB signaling and thereby elevating the expression of lncRNA ANRIL.

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