RESUMEN
Radiotherapy is a crucial approach for treating tumors. However, radiation-induced aseptic inflammation is a common complication. Radiation pneumonitis is the acute manifestation of radiation-induced lung disease, and interleukin 6 (IL-6) is a major proinflammatory cytokine involved in radiation-induced lung injury. Here we found that silencing Zinc finger and BTB domain-containing protein 7B (Zbtb7b) resulted in higher radiation-induced IL-6 production in THP1 cells and BEAS-2B lung bronchial epithelial cells. Mechanistically, Zbtb7b recruited RNA demethylase ALKBH5 to IL6 mRNA. Subsequentially, it demethylated N6-methyladenosine (m6A) modification of IL6 mRNA and inhibited its nuclear export. Thus, Zbtb2b epigenetically suppresses irradiation-induced IL-6 production in the lungs via inhibiting the m6A modification and nucleocytoplasmic transport of IL6 mRNA, serving as a new potential predictive marker and therapeutic target in radiation pneumonitis treatment.
Asunto(s)
Adenosina/análogos & derivados , Proteínas de Unión al ADN/genética , Inflamación/genética , Interleucina-6/genética , ARN Mensajero/genética , Factores de Transcripción/genética , Adenosina/genética , Línea Celular , Epigénesis Genética , Células Epiteliales/metabolismo , Células Epiteliales/efectos de la radiación , Silenciador del Gen , Células HEK293 , HumanosRESUMEN
Three new ergostane steroids, 7α-acetoxyl-ergosta-5,24(28)-diene-3ß,4ß,20S-triol (1), 7α-acetoxyl-ergosta-5,24(28)-diene-3ß,4ß-diol (2), and 7α-acetoxyl-ergosta-5,24(28)-3ß-ol (3) were isolated from the ethanol extract of stem bark of Dysoxylum mollissimum BI. Structural elucidation of all the compounds was performed by spectral methods such as 1D and 2D (1H-1H COSY, HMQC, and HMBC) NMR spectroscopy, in addition to high resolution mass spectrometry. All the isolated steroids were in vitro evaluated for their anti-inflammatory activity against COX-1 and COX-2. As a result, steroids 1-3 exhibited modest selective inhibition for COX-1 (>60%).
Asunto(s)
Ergosterol/análogos & derivados , Meliaceae/química , Extractos Vegetales/química , Esteroides/química , Animales , Antiinflamatorios/química , Antiinflamatorios/farmacología , Línea Celular , Ergosterol/química , Estructura Molecular , Corteza de la Planta/química , Extractos Vegetales/farmacología , Tallos de la Planta/química , Esteroides/farmacologíaRESUMEN
Phytochemical investigation on the 70% ethanol extract of the leaves of Alstonia mairei resulted in the isolation of three new monoterpenoid indole alkaloids, alstomairines A-C (1-3), along with one known compound, alpneumine A (4). Structural elucidation of all the compounds was accomplished by spectral methods such as 1D and 2D NMR, IR, UV, and HRESIMS. The isolated compounds were tested in vitro for cytotoxic activities against four osteosarcoma cell lines. Consequently, alkaloids 2 and 3 exhibited cytotoxic activities for all tested tumor cell lines with IC50 values from 9.2 to 13.0 µM.