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Beneficial influence of activation of TLR3 and RIG-I signaling pathways on bacterium-elimination barrier effect caused by polyinosinic-polycytidylic acid

A technology of polyinosinic acid and signaling pathways, applied in the field of bacterial clearance of barrier effects

Inactive Publication Date: 2017-05-31
宁波美丽人生医药生物科技发展有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Furthermore, the deleterious effects of polyinosinic acid may be mediated by type I interferons

Method used

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  • Beneficial influence of activation of TLR3 and RIG-I signaling pathways on bacterium-elimination barrier effect caused by polyinosinic-polycytidylic acid
  • Beneficial influence of activation of TLR3 and RIG-I signaling pathways on bacterium-elimination barrier effect caused by polyinosinic-polycytidylic acid
  • Beneficial influence of activation of TLR3 and RIG-I signaling pathways on bacterium-elimination barrier effect caused by polyinosinic-polycytidylic acid

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0052] Polycytoglycine reduces bacterial clearance

[0053] We first examined the effect of polysinosinate administration on bacterial clearance following bacterial infection. The experimental animals were given intranasal administration of polyinosine or imiquimod for two consecutive days (ie, twice). On the third day (i.e., 24 hours after the last polyinosine dose), animals were injected intrathecally with S. pneumoniae. We found a significant increase in bacterial counts in the lungs of animals administered nasal polyinosinosinate. Interestingly, imiquimod or gademotel (TLR7 agonists such as figure 1 A) There was no significant difference in bacterial clearance between the treatment groups. But both groups showed robust clearance during the initial challenge phase. Administration of TLR7 ligand alone was therefore not sufficient to reduce bacterial clearance.

[0054] Second, we examined whether polyinosinogenic acid also reduced the clearance of another important cli...

Embodiment 2

[0056] Polyinosinogenic acid increases susceptibility of lung tissue to bacteria

[0057] Second, we examined whether polyinosinogenic acid also reduced the clearance of another important clinical pathogen causing viral secondary bacterial pneumonia, methicillin-resistant Staphylococcus aureus (MRSA). Similar to the above category, after 24h of Staphylococcus aureus infection, administration of polysinosinic acid will reduce its clearance rate ( figure 1 B). Thus, polyinosinogenic acid appears to impair host lung tissue defense mechanisms against two pathogens clinically responsible for viral secondary bacterial pneumonia, Streptococcus pneumoniae and methicillin-resistant Staphylococcus aureus.

Embodiment 3

[0059] Duration of post-administration of polyinosinosa and risk of bacterial infection

[0060] Second, we observed the time point at which the bacterial clearance rate decreased in the animal body after the administration of polyinosinogenic acid. Since viral infections, such as influenza, usually last for several days or even longer, we conducted related experimental studies, taking polyinosinogenic acid in 1 dose or 3 doses to simulate the effect of viral infection. After 24 hours of intranasal administration of polyinosinogenic acid or saline once or three times, the experimental animals were intrathecally injected with Streptococcus pneumoniae. At 48h, record the amount of bacteria in the body. We found that the dose of polysarcocytate correlates with the rate of bacterial clearance. The bacterial clearance rate in the experimental animals with one-time administration of polyinosinic acid will tend to decrease (the average CFU value is 8 times higher than that of the n...

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Abstract

The invention especially relates to beneficial influence of activation of TLR3 and RIG-I signaling pathways on bacterium-elimination barrier effect caused by polyinosinic-polycytidylic acid, belonging to the field of biological medicine. According to the invention, a virus-immune mouse model is simulated, and TLR3-gene-knocked mice, Cardif-gene-knocked mice and TLR3-and-Cardif-gene-knocked mice are dosed with polyinosinic-polycytidylic acid; and final results prove that activation of the TLR3 and RIG-I signaling pathways exerts effect in alleviating bacterium-elimination barrier effect on the lung of a host caused by polyinosinic-polycytidylic acid.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to the activation of TLR3 and RIG-I signaling pathways to contribute to the effect of polyinosinic acid-induced bacteria clearance barriers. Background technique [0002] Respiratory viral infections are common and often exhibit a benign clinical course. However, a significant proportion of patients develop concomitant or secondary bacterial infection, a complication that can lead to respiratory failure or death. Although outbreaks of such complications are highest in children, the elderly, and immunosuppressed populations, viral bacterial pneumonia can also occur in healthy adults and result in a significant disease burden. Viral-bacterial pneumonia has been repeatedly reported following the prevalence of influenza infection. It was the leading cause of death in patients during the influenza epidemics of the 20th century and the 2009 H1N1 influenza pandemic. [0003] The mechanisms by...

Claims

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Application Information

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IPC IPC(8): A61K49/00
Inventor 田晓丽
Owner 宁波美丽人生医药生物科技发展有限公司
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