RESUMO
Ulcerative colitis （UC）is a chronic inflammatory bowel disease caused by multiple factors ，and its etiology and pathogenesis remain unclear . Tofacitinib，a small molecule rapidly absorbed by oral administration ，treats UC primarily by inhibiting Janus kinase （JAK）. Tofacitinib has been approved by the FDA and the European Medicines Agency for the treatment of moderate to severe UC . Many clinical studies on tofacitinib in the treatment of UC have been carried out abroad ，but there is no relevant report on its use in UC in China . This paper summarizes the relevant research advances of tofacitinib in the treatment of UC from its mechanism ，clinical application and safety . The results show that tefatinib mainly treats UC by inhibiting the expression of JAK and proinflammatory factors , regulating the overexpressed signaling transducers and activators of transcription , and repairing the intestinal mucosal barrier . Tofacitinib has good clinical efficacy ，but safety studies have shown that the risks of herpes zoster and thrombosis should not be ignored ，and the drug should be used with caution in pregnant ，children，adolescents， and elderly patients . The efficacy and safety of tofacitinib in Chinese population should be further studied in the future ，since it has not been used in UC patients in China .
RESUMO
Oligodendrocytes (OLs) are myelinating glial cells that form myelin sheaths around axons to ensure rapid and focal conduction of action potentials. Here, we found that an axonal outgrowth regulatory molecule, AATYK (apoptosis-associated tyrosine kinase), was up-regulated with OL differentiation and remyelination. We therefore studied its role in OL differentiation. The results showed that AATYK knockdown inhibited OL differentiation and the expression of myelin genes in vitro. Moreover, AATYK-deficiency maintained the proliferation status of OLs but did not affect their survival. Thus, AATYK is essential for the differentiation of OLs.
Assuntos
Animais , Camundongos , Ratos , Animais Recém-Nascidos , Proteínas Reguladoras de Apoptose , Genética , Metabolismo , Diferenciação Celular , Fisiologia , Proliferação de Células , Genética , Células Cultivadas , Cuprizona , Toxicidade , Doenças Desmielinizantes , Metabolismo , Patologia , Embrião de Mamíferos , Regulação da Expressão Gênica no Desenvolvimento , Genética , Antígeno Ki-67 , Metabolismo , Camundongos Endogâmicos C57BL , Proteína Básica da Mielina , Metabolismo , Proteína Proteolipídica de Mielina , Metabolismo , Bainha de Mielina , Metabolismo , Oligodendroglia , Metabolismo , Proteínas Tirosina Quinases , Genética , Metabolismo , RNA Interferente Pequeno , Genética , Metabolismo , Ratos Sprague-DawleyRESUMO
Objective To study the influence factors of the release rate of benorilate from sustained release matrix tablets. Methods The matrix tablets of benorilate were prepared by using hydroxypropylmethylcellulose (HPMC) as the matrix material. The effects of the contents of HPMC, polyvinyl pyrrolidone (PVP), and microcrystaline cellulose (MCC), and the method of preparation on in vitro drug release were studied by evaluating the n value in the Peppas equation. Results The increasing HPMC content led to decrease of benorilate release. However, PVP and MCC used in this experiment accelerated the benorilate release from the tablets. The drug released from the tablet prepared by dry method was faster than that by wet method. Conclusion The contents of HPMC, PVP, and MCC, especially HPMC, have effects on the release rate of benorilate, but the two preparation methods have less effect.