RESUMO
Cardiovascular diseases have become the leading cause of death in urban and rural areas. Myocardial fibrosis is a common pathological manifestation at the adaptive and repair stage of cardiovascular diseases, easily predisposing to cardiac death. Non-coding RNAs (ncRNAs), RNA molecules with no coding potential, can regulate gene expression in the occurrence and development of myocardial fibrosis. Recent studies have suggested that Chinese herbal medicine can relieve myocardial fibrosis through targeting various ncRNAs, mainly including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Thus, ncRNAs are novel drug targets for Chinese herbal medicine. Herein, we summarized the current understanding of ncRNAs in the pathogenesis of myocardial fibrosis, and highlighted the contribution of ncRNAs to the therapeutic effect of Chinese herbal medicine on myocardial fibrosis. Further, we discussed the future directions regarding the potential applications of ncRNA-based drug screening platform to screen drugs for myocardial fibrosis.
RESUMO
Overactivation or overexpression of ß-catenin in the Wnt (wingless) signaling pathway plays an important role in tumorigenesis. Interaction of ß-catenin with T-cell factor (Tcf) DNA binding proteins is a key step in the activation of the proliferative genes in response to upstream signals of this Wnt/ß-catenin pathway. Recently, we identified a new small molecule inhibitor, named BC21 (C(32)H(36)Cl(2)Cu(2)N(2)O(2)), which effectively inhibits the binding of ß-catenin with Tcf4-derived peptide and suppresses ß-catenin/Tcf4 driven reporter gene activity. This inhibitor decreases the viability of ß-catenin overexpressing HCT116 colon cancer cells that harbor the ß-catenin mutation, and more significantly, it inhibits the clonogenic activity of these cells. Down-regulation of c-Myc and cyclin D1 expression, the two important effectors of the Wnt/ß-catenin signaling, is confirmed by treating HCT116 cells with BC21. This compound represents a new and modifiable potential anticancer candidate that targets ß-catenin/Tcf-4 interaction.
Assuntos
Antineoplásicos/farmacologia , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Avaliação Pré-Clínica de Medicamentos/métodos , Bibliotecas de Moléculas Pequenas/farmacologia , Fatores de Transcrição/metabolismo , beta Catenina/metabolismo , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/química , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cristalografia por Raios X , Regulação para Baixo/efeitos dos fármacos , Células HCT116 , Humanos , Modelos Moleculares , Ligação Proteica/efeitos dos fármacos , Conformação Proteica , Fator de Transcrição 4 , Fatores de Transcrição/química , Transcrição Gênica/efeitos dos fármacos , Interface Usuário-Computador , Via de Sinalização Wnt/efeitos dos fármacos , Via de Sinalização Wnt/genética , beta Catenina/química , beta Catenina/genéticaRESUMO
Two natural triterpenoid saponins bearing N-acetylglucosamine, lotoidoside D and lotoidoside E, which had been available only from Glinus lotoides growing in Egyptian desert, were facilely synthesized from readily available oleanolic acid. Preliminary pharmacological research showed their antitumor activity against HeLa cell.