RESUMO
cGAS-STING signaling is essential for innate immunity. Its misregulation promotes cancer or autoimmune and autoinflammatory diseases, and it is imperative to identify effective lead compounds that specifically downregulate the pathway. We report here that astin C, a cyclopeptide isolated from the medicinal plant Aster tataricus, inhibits cGAS-STING signaling and the innate inflammatory responses triggered by cytosolic DNAs. Moreover, mice treated with astin C are more susceptible to HSV-1 infection. Consistently, astin C markedly attenuates the autoinflammatory responses in Trex1-/- BMDM cells and in Trex1-/- mouse autoimmune disease model. Mechanistically, astin C specifically blocks the recruitment of IRF3 onto the STING signalosome. Collectively, this study characterizes a STING-specific small-molecular inhibitor that may be applied for potentially manipulating the STING-mediated clinical diseases.
Assuntos
Imunidade Inata/efeitos dos fármacos , Proteínas de Membrana/metabolismo , Nucleotídeos/metabolismo , Peptídeos Cíclicos/farmacologia , Animais , Anti-Infecciosos/metabolismo , Doenças Autoimunes/tratamento farmacológico , Citosol/metabolismo , DNA/metabolismo , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Células HEK293 , Herpesvirus Humano 1/efeitos dos fármacos , Humanos , Inflamação/patologia , Fator Regulador 3 de Interferon/metabolismo , Listeria monocytogenes/efeitos dos fármacos , Masculino , Proteínas de Membrana/química , Camundongos , Camundongos Endogâmicos C57BL , Peptídeos Cíclicos/química , Peptídeos Cíclicos/uso terapêutico , Células RAW 264.7 , Transdução de SinaisRESUMO
OBJECTIVE: This study aims to discuss the correlation between daily reported H7N9 cases and stock price indices in China. METHODS: Information on daily reported H7N9 cases and stock market sectors indices between February 19, 2013 and March 31, 2014 were collected. A distributed lag non-linear model was used to describe the variation trend for the stock indices. RESULTS: The daily reported number of H7N9 cases was associated with the closing price of the Avian Influenza Sector Index (P < 0.05) and the opening price of the Shanghai Composite Index (P = 0.029). The Avian Influenza Sector Index decreased with increasing of daily reported case number when daily reported cases ≤ 4. Case number was associated with the opening/closing price of the Chinese Traditional Medicine Sector Index, the Biological Product Sector Index, and the Biomedicine Sector Index (P < 0.05). CONCLUSION: New or reemerging infectious diseases epidemic cause economic loss which is reflected in movements in stock prices.
RESUMO
BACKGROUND: Astragaloside â £ (ASG-â £, (Fig. 1) is the most active component of Chinese sp. Astragalus membranaceus Bunge (Fabaceae) that has showed antioxidant, antiapoptotic and antiviral activities among others. It is reported to play an important role in cardiac fibrosis (CF), but the mechanism remains unclear. PURPOSE: To investigate the mechanism of ASG-â £ on inhibiting myocardial fibrosis induced by hypoxia. STUDY DESIGN: We studied the relationship between anti-fibrotic effect of ASG-â £ and transient receptor potential cation channel, subfamily M, member 7 (TRPM7) by in vivo and in vitro experiments. METHODS: In vivo, CF was induced by subcutaneous isoproterenol (ISO) for 10 days. Rat hearts were resected for histological experiment and reverse transcription real-time quantitative poly merase chain reaction (RT-qPCR). In vitro, molecular and cellular biology technologies were used to confirm the anti-fibrosis effect underlying mechanism of ASG-â £. RESULTS: Histological findings and the collagen volume fraction showed that ASG-â £ decreased fibrosis in heart tissues. Hypoxia could stimulate the proliferation and differentiation of cardiac fibroblast which indicated that the degree of fibrosis was increased significantly. Anoxic treatment could also obviously up-regulate the expression of TRPM7 protein and current. ASG-â £ groups showed the opposite results. Knock-down TRPM7 experiment further confirmed the role of TRPM7 channel in hypoxia-induced cardiac fibrosis. CONCLUSION: Our results suggest that the inhibition of hypoxia-induced CF in vivo and in vitro by ASG-IV is associated with reduction of the expression of TRPM7. The moderate inhibition of the TRPM7 channel may be a new strategy for treating cardiac fibrosis.
Assuntos
Fibrose Endomiocárdica/tratamento farmacológico , Fibrose Endomiocárdica/metabolismo , Saponinas/farmacologia , Canais de Cátion TRPM/metabolismo , Triterpenos/farmacologia , Animais , Diferenciação Celular/efeitos dos fármacos , Hipóxia Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Fibrose Endomiocárdica/induzido quimicamente , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Coração/efeitos dos fármacos , Isoproterenol/farmacologia , Isoproterenol/toxicidade , Masculino , Camundongos , Células NIH 3T3/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Canais de Cátion TRPM/genética , Regulação para CimaRESUMO
Antioxidant extracts from 5 potato lines were evaluated for antioxidant activity, total phenolics, chlorogenic acid, anthocyanin content, and in vitro anticancer capacity. Analysis showed that Mexican wild species S. pinnatisectum had the highest antioxidant activity, total phenolic, and chlorogenic acid content. The proliferation of colon cancer and liver cancer cells was significantly inhibited by potato antioxidant extracts. The highest antiproliferative activity was observed in extracts of S. pinnatisectum and the lowest in Northstar. An inverse correlation was found between total phenolics and the EC(50) of colon cancer cell (R(2) = 0.9303), as well as liver cancer cell proliferation (R(2) = 0.8992). The relationship between antioxidant activity and EC(50) of colon cancer/liver cancer cell proliferation was significant (R(2) = 0.8144; R(2) = 0.956, respectively). A significant difference in inhibition of cancer cells (P < 0.01) existed between the 3 polyphenols: chlorogenic acid, pelargonidin chloride, and malvidin chloride, suggesting that chlorogenic acid was a critical factor in the antiproliferation of colon cancer and liver cancer cells.