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1.
Bosn J Basic Med Sci ; 22(3): 302-314, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34627135

RESUMO

With the continuous development of drug screening technology, new screening methodologies and technologies are constantly emerging, driving drug screening into rapid, efficient and high-throughput development. Microfluidics is a rising star in the development of innovative approaches in drug discovery. In this article, we summarize the recent years' progress of microfluidic chip technology in drug screening, including the developmental history, structural design, and applications in different aspects of microfluidic chips on drug screening. Herein, the existing microfluidic chip screening platforms are summarized from four aspects: chip structure design, sample injection and drive system, cell culture technology on a chip, and efficient remote detection technology. Furthermore, this review discusses the application and developmental prospects of using microfluidic chips in drug screening, particularly in screening natural product anticancer drugs based on chemical properties, pharmacological effects, and drug cytotoxicity.


Assuntos
Técnicas de Cultura de Células , Microfluídica , Avaliação Pré-Clínica de Medicamentos/métodos
2.
Diabetes ; 66(3): 663-673, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28028078

RESUMO

Whether neuronal inositol-requiring enzyme 1 (Ire1) is required for the proper regulation of energy balance and glucose homeostasis is unclear. We found that pro-opiomelanocortin (Pomc)-specific deficiency of Ire1α accelerated diet-induced obesity concomitant with a decrease in energy expenditure. This hypometabolic phenotype included deficits in thermogenic responses to diet and cold exposure as well as "beiging" of white adipose tissue. We also demonstrate that loss of Ire1α in Pomc neurons impaired whole-body glucose and insulin tolerance as well as hepatic insulin sensitivity. At the cellular level, deletion of Ire1α in Pomc neurons elevated hypothalamic endoplasmic reticulum (ER) stress and predisposed Pomc neurons to leptin and insulin resistance. Together, the current studies extend and confirm conclusions that Ire1α-Xbp1s and associated molecular targets link ER stress in arcuate Pomc neurons to aspects of normal energy and glucose homeostasis.


Assuntos
Glicemia/metabolismo , Estresse do Retículo Endoplasmático/genética , Endorribonucleases/genética , Metabolismo Energético/genética , Neurônios/metabolismo , Proteínas Serina-Treonina Quinases/genética , Termogênese/genética , Proteína 1 de Ligação a X-Box/metabolismo , Animais , Núcleo Arqueado do Hipotálamo/citologia , Núcleo Arqueado do Hipotálamo/metabolismo , Western Blotting , Temperatura Baixa , Glucose/metabolismo , Teste de Tolerância a Glucose , Homeostase/genética , Hipotálamo/metabolismo , Imuno-Histoquímica , Resistência à Insulina/genética , Leptina/metabolismo , Masculino , Camundongos , Técnicas de Patch-Clamp , Pró-Opiomelanocortina/metabolismo , Reação em Cadeia da Polimerase em Tempo Real
3.
J Chromatogr A ; 1364: 53-8, 2014 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-25218628

RESUMO

In this study, graphitic carbon nitride (g-C3N4) was used as a coating material for solid-phase microextraction (SPME) applications. Coupled to gas chromatography (GC), the extraction ability of the SPME fiber was investigated and compared with the commercial fibers of 100 µm PDMS and 85 µm CAR/PDMS using six target analytes including deltamethrin, nerolidol, amphetamine, dodecane, ametryn and acrylamide. The g-C3N4 coating revealed excellent extraction ability and durability comparing with those of the commercial fibers due to its loose structure and unique physicochemical properties. The repeatability for each single fiber was found to be 3.46% and reproducibility for fiber to fiber was 8.53%. The g-C3N4 SPME fiber was applied to the determination of acrylamide in potato chips, the linearity and detection limit was 0.5-250 µg g(-1) and 0.018 µg g(-1), respectively.


Assuntos
Nitrilas/química , Microextração em Fase Sólida/instrumentação , Acrilamida/análise , Cromatografia Gasosa , Análise de Alimentos , Limite de Detecção , Reprodutibilidade dos Testes , Resinas Sintéticas/química , Solanum tuberosum/química , Microextração em Fase Sólida/métodos , Triazinas/química
4.
Peptides ; 50: 129-38, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24140860

RESUMO

LL-37 is the single cathelicidin host defense peptide in humans with direct antimicrobial and immunomodulatory activities. Specific regulation of LL-37 synthesis has emerged as a novel non-antibiotic approach to disease control and prevention. Short-chain fatty acids, and butyrate in particular, were found recently to be strong inducers of LL-37 gene expression without causing inflammation. Here, we further evaluated the LL-37-inducing efficiency of a broad range of saturated free fatty acids and their derivatives in human HT-29 colonic epithelial cells and U-937 monocytic cells by real-time RT-PCR. Surprisingly, we revealed that valerate, hexanoate, and heptanoate with 5-7 carbons are more potent than 4-carbon butyrate in promoting LL-37 gene expression in both cell types. Free fatty acids with longer than 7 or shorter than 4 carbons showed only a marginal effect on LL-37 expression. Studies with a series of fatty acid derivatives with modifications in the aliphatic chain or carboxylic acid group yielded several analogs such as benzyl butyrate, trans-cinnamyl butyrate, glyceryl tributyrate, and phenethyl butyrate with a comparable LL-37-inducing activity to sodium butyrate. On the other hand, although reactive, the anhydride derivatives of short- and medium-chain fatty acids are as potent as their corresponding free acid forms in LL-37 induction. Thus, these newly identified free fatty acids and their analogs with a strong capacity to augment LL-37 synthesis may hold promise as immune boosting dietary supplements for antimicrobial therapy.


Assuntos
Anti-Infecciosos/farmacologia , Peptídeos Catiônicos Antimicrobianos/agonistas , Butiratos/farmacologia , Células Epiteliais/efeitos dos fármacos , Fatores Imunológicos/farmacologia , Monócitos/efeitos dos fármacos , Anti-Infecciosos/química , Peptídeos Catiônicos Antimicrobianos/biossíntese , Peptídeos Catiônicos Antimicrobianos/genética , Butiratos/química , Caproatos/química , Caproatos/farmacologia , Linhagem Celular Tumoral , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Expressão Gênica/efeitos dos fármacos , Ácidos Heptanoicos/química , Ácidos Heptanoicos/farmacologia , Humanos , Fatores Imunológicos/química , Monócitos/citologia , Monócitos/metabolismo , Ácidos Pentanoicos/química , Ácidos Pentanoicos/farmacologia , Relação Estrutura-Atividade , Catelicidinas
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