RESUMEN
Fourteen new 2-benzylbenzofuran O-glycosides (1-13, 15) and one new key precursor, diarylacetone (14) were isolated from the roots of Heterosmilax yunnanensis Gagnep, which all have characteristic 2,3,4-O-trisubstituted benzyl. Their structures were elucidated by 1D and 2D NMR, HRESIMS, UV and IR. The isolated compounds were assessed for their cardioprotective activities and compounds 1, 3 and 6 could significantly improve cardiomyocytes viability. Moreover, the mechanistic study revealed that these three compounds could significantly decrease intracellular ROS levels and maintain mitochondrial homeostasis upon hypoxia inducement. Consequently, 1, 3 and 6 might serve as potential lead compounds to prevent myocardial ischemia.
Asunto(s)
Benzofuranos , Glicósidos , Raíces de Plantas , Glicósidos/farmacología , Glicósidos/química , Espectroscopía de Resonancia Magnética , Estructura Molecular , Raíces de Plantas/química , Benzofuranos/química , Benzofuranos/farmacologíaRESUMEN
Notch signaling is highly conserved in most animals and plays critical roles during neurogenesis as well as embryonic development. Synthetic Notch-based systems, modeled from Notch receptors, have been developed to sense and respond to a specific extracellular signal. Recent advancement of synNotch has shown promise for future use in cellular engineering to treat cancers. However, synNotch from Morsut et al. (2016) has a high level of ligand-independent activation, which limits its application. Here we show that adding an intracellular hydrophobic sequence (QHGQLWF, named as RAM7) present in native Notch, significantly reduced ligand-independent activation. Our enhanced synthetic Notch receptor (esNotch) demonstrates up to a 14.6-fold reduction in ligand-independent activation, without affecting its antigen-induced activation efficiency. Our work improves a previously reported transmembrane receptor and provides a powerful tool to develop better transmembrane signaling transduction modules for further advancement of eukaryotic synthetic biology.
Asunto(s)
Ingeniería Celular/métodos , Receptores Artificiales/química , Receptores Artificiales/metabolismo , Receptores Notch/química , Receptores Notch/metabolismo , Secuencia de Aminoácidos , Antígenos/metabolismo , Membrana Celular/metabolismo , Clonación Molecular/métodos , Células HEK293 , Humanos , Ligandos , Plásmidos/genética , Dominios Proteicos , Proteolisis , Receptores Notch/genética , Transducción de Señal/genética , Anticuerpos de Cadena Única , Biología Sintética/métodos , TransfecciónRESUMEN
PURPOSE: This study explored the clinical characteristics, diagnosis and treatments of primary blepharospasm. METHODS: In this retrospective analysis, 100 patients with blepharospasm were enrolled. Data were collected from medical records and face-to-face interviews with patients and their families. RESULTS: The age of onset was 56.4 ± 2.7 (range, 32-76 years). The duration between onset and accurate diagnosis was 38.7 ± 36.0 months (range, 2-120 months). Dry eyes occurred in 54% of the patients. The initial diagnostic accuracy was 10%. Dry eye syndrome, conjunctivitis/keratitis and myasthenia gravis caused the most confusion in the differential diagnosis. Regular botulinum toxin type A injections improved both eyelid spasms and subjective ocular symptoms in all patients. CONCLUSIONS: Regular botulinum toxin type A injections improved both eyelid spasms and subjective ocular symptoms in blepharospasm patients. The differentiation of primary blepharospasm differentiation from dry eye syndrome, conjunctivitis/keratitis and myasthenia gravis must be improved.