Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
-
Intratracheal (IT) lipopolysaccharide (LPS) causes severe acute lung injury (ALI) and systemic inflammation. CMT-3 has pleiotropic anti-inflammatory effects including matrix metalloproteinase (MMP) inhibition, attenuation of neutrophil (PMN) activation, and elastase release. CMT-3's poor water solubility limits its bioavailability when administered orally for treating ALI. We developed a nano-formulation of CMT-3 (nCMT-3) to test the hypothesis that the pleiotropic anti-inflammatory activities of IT nCMT-3 can attenuate LPS-induced ALI. ⋯ Pre-treatment with nCMT3 significantly attenuates LPS-induced lung injury/inflammation by multiple mechanisms including: MMP activation, PMN elastase, sTREM-1 release, and NLRP3 inflammasome/caspase-1 activation.
-
Platelet distribution width (PDW) and PDW-to-platelet ratio (PPR) have been proven to be good prognostic indicators for many diseases. However, their prognostic values in severe burns have not been reported. ⋯ PDW and PPR on day 3 and day 7 were independent risk factors for 120-day mortality in severe burn patients. These objective and readily available prognostic indicators may be more clinically favored.
-
Septic cardiomyopathy increases mortality by 70% to 90% and results in mechanical dysfunction of cells. ⋯ LPS-induced contraction dysfunction and the reversal effects of rhAPC were successfully assessed by the mechanical properties of mESC-CMs. The CellDrum technology proved a decent tool to simulate sepsis in-vitro.
-
C1q/tumor necrosis factor-related protein 1 (CTRP1) has been demonstrated as a crucial regulator in myocardial injury (MI). The present study aims to evaluate the mechanism of CTRP1 in sepsis-induced MI. The septic mouse model was established via cecal ligation and puncture and the in vitro cell model was established via lipopolysaccharide treatment. ⋯ Nrf2 overexpression promoted CTRP1 expression via binding to the CTRP1 promotor and suppressed cardiomyocyte pyroptosis. CTRP1 downregulation abolished the inhibitory effect of Nrf2 overexpression on cardiomyocyte pyroptosis. Overall, Nrf2 promoted CTRP1 expression via binding to the CTRP1 promotor to inhibit cardiomyocyte pyroptosis, thereby alleviating MI in septic mice.
-
Skeletal muscles play important roles in innate immunity. However, in vitro, their sensitivity to LPS is low. In other tissues, LPS sensing is facilitated by the presence of plasma, LPS binding protein (LBP), or soluble CD14 (sCD14). ⋯ LBP supplementation did not augment secretion; however, 1% plasma from CD14-/- mice suppressed cytokine/chemokine secretion from EDL muscle. In conclusion, intact slow and fast mouse muscles have similar cytokine/chemokine responses to LPS but depend on the presence of low levels of plasma constituents. Though sCD14 plays some role in EDL muscle, neither sCD14 nor LBP can fully account for the strong effects of plasma on LPS sensitivity.