trans-4-(Aminomethyl)cyclohexane carboxylic acid methylamide (t-AMCHA methylamide) inhibits the physical interaction between urokinase-type plasminogen activator and stratum corneum, and accelerates the recovery of barrier function
“…Katsuta et al . reported that TA could inhibit the physical interaction between urokinase‐type plasminogen activator and stratum corneum, which is the reason for the accelerating recovery of barrier function . However, there seems to be no direct evidence of TJ functioning as an intercellular permeability barrier under the TA repair experiments for both the SLS application and UVB irritation.…”
These experiments suggest that TA can accelerate skin barrier recovery and upregulate occludin induced by physicochemical damages of human skin, but it is advisable to perform more research on the upregulation of occludin in molecular mechanism in the future.
“…Katsuta et al . reported that TA could inhibit the physical interaction between urokinase‐type plasminogen activator and stratum corneum, which is the reason for the accelerating recovery of barrier function . However, there seems to be no direct evidence of TJ functioning as an intercellular permeability barrier under the TA repair experiments for both the SLS application and UVB irritation.…”
These experiments suggest that TA can accelerate skin barrier recovery and upregulate occludin induced by physicochemical damages of human skin, but it is advisable to perform more research on the upregulation of occludin in molecular mechanism in the future.
“…[16][17][18] Finally, further justification for the selection of tranexamic derivatives in this work comes from the fact that they have been used as antifibrinolytic drugs with no sign of cytotoxicity. [19][20][21] Herein, we report the design and the synthesis of a series of DOTA conjugates (4a-c) and their Gd-complexes of the type [Gd(L)(H 2 O)] 3 xH 2 O (5a-c, L = 4a-c) for use as a new class of bifunctional MRI CAs with liver-specific and blood-pool properties.…”
Gd-complexes of the type [Gd(L)(H(2)O)]·xH(2)O (5a-c), where L is DOTA conjugates of tranexamic acid (4a) and tranexamic esters (4b,c), have been prepared as a new class of MRI blood-pool contrast agents (BPCAs). Thermodynamic stability (K(GdL)) and pharmacokinetic inertness of 5 compare well with or better than those of analogous MRI contrasting agents (CAs) such as Gd-DOTA and Gd-DTPA-BMA. Their R(1)-relaxivities are significantly higher than those of any of the clinically used MRI CAs. T(1)-weighted MR images of mice administered by 5c demonstrate high blood-pool effect with simultaneous contrast enhancement in liver. The structural uniqueness of 5c lies in the fact that it adopts macrocyclic DOTA instead of acyclic DTPA. In addition, 5c is nonionic and makes no resort to aromatic substituent(s) in the chelate backbone for the blood-pool enhancement. The nature of hepatobiliary uptake demonstrated by 5c may be explained in terms of lipophilicity of tranexamate in the chelate (4c). The cell cytotoxicity test shows no toxicity found with 5, suggesting their use as a practical MRI BPCAs.
“…Based on previous studies showing that urokinase-type plasminogen activator is associated with barrier function in human skin 5 , 6 and that tranexamic acid, a plasminogen inhibitor, accelerates skin barrier recovery 2 , 7 , we initially expected that the impairment of human skin barrier function by Cry j1 would be due to plasminogen activation. Therefore, we examined the expression of plasminogen and plasmin by RT-PCR.…”
We previously demonstrated that Cry j1, the major pollen allergen of Cryptomeria japonica (Japanese cedar), transiently increases protease activity and intracellular Ca2+ concentration in cultured human keratinocytes, and delays recovery after stratum corneum barrier disruption in human skin ex vivo. Topical application of tranexamic acid or trypsin-type serine protease inhibitors accelerates barrier recovery. We hypothesized that tranexamic acid might prevent the transient protease activity increase and the barrier recovery delay induced by Cry j1. Here, we tested this hypothesis and examined the mechanism involved. In cultured human keratinocytes, knock-down of protease-activated receptor 1 (PAR-1) reduced the transient increase of calcium induced by Cry j1, whereas knock-down of PAR-2 did not. Knock-down of thrombin significantly reduced the transient increases of calcium concentration and protease activity. Tranexamic acid, soybean trypsin inhibitor, or bivalirudin (a thrombin inhibitor) also reduced the calcium elevation induced by Cry j1 and/or thrombin. Co-application of tranexamic acid or bivalirudin with Cry j1 to human skin ex vivo blocked the delay of barrier recovery. These results suggest that thrombin and PAR-1 or PAR-1-like receptor might mediate the adverse effects of Cry j1 on human epidermal keratinocytes, and could open up a new strategy for treating inflammatory skin diseases.
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