Use the labels in the right column to find what you want. Or you can go thru them one by one, there are only 31,919 posts. Searching is done in the search box in upper left corner. I blog on anything to do with stroke. DO NOT DO ANYTHING SUGGESTED HERE AS I AM NOT MEDICALLY TRAINED, YOUR DOCTOR IS, LISTEN TO THEM. BUT I BET THEY DON'T KNOW HOW TO GET YOU 100% RECOVERED. I DON'T EITHER BUT HAVE PLENTY OF QUESTIONS FOR YOUR DOCTOR TO ANSWER.
Saturday, February 15, 2025
Targeted codelivery of nitric oxide and hydrogen sulfide for enhanced antithrombosis efficacy
Didn't your competent? doctor start working on protocols for these years ago? NO? So, you DON'T HAVE A FUNCTIONING STROKE DOCTOR, DO YOU?
We develope an enzyme‒prodrug system for the targeted codelivery of NO and H2S with reduced side effects caused by systemic delivery.
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Optimized combination of NO and H2S with a low combination index synergistically inhibitsplatelet adhesion and activation.
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Targeted codelivery of NO and H2S demonstrates enhanced therapeutic efficacy for thrombosis in two mousemodels of thrombosis.
Abstract
Thrombosis
is a leading cause of mortality worldwide. As important gaseous
signaling molecules, both nitric oxide (NO) and hydrogen sulfide (H2S)
demonstrate antiplatelet and anticoagulant functions, but little
attention has been given to their synergistic effect and the underlying
mechanism. In the present study, we developed an NO/H2S
codelivery system based on enzyme prodrug therapy (EPT) strategy in
which the prodrugs are specifically recognized by the engineered
β-galactosidase. Targeted codelivery of NO and H2S in vivo
was demonstrated by near-infrared fluorescence imaging and confirmed by
measuring plasma and tissue levels; as a result, the side effects
caused by systemic delivery, such as bleeding time, were reduced.
Delivery of an optimized combination of NO and H2S with a low
combination index (CI) results in a synergistic effect on the
inhibition of platelet adhesion and activation. Mechanistically, NO and H2S
cooperatively enhance the cGMP level through redox-based
posttranslational modifications of phosphodiesterase 5A (PDE5A), which
leads to activation of the cGMP/PKG signaling pathway. Furthermore,
targeted codelivery of NO and H2S demonstrates enhanced therapeutic efficacy for thrombosis in two mouse models of FeCl3-induced arterial thrombosis and deep vein thrombosis. Collectively, these results confirm the synergistic efficacy of NO and H2S
for antithrombotic therapy, and the codelivery system developed in this
study represents a promising candidate for clinical translation.
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