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
-
Acute kidney injury (AKI) can result from renal ischemia and reperfusion (I/R) and often occurs during surgical procedures in cardiac, liver, kidney transplantation and trauma-hemorrhage. Milk fat globule epidermal growth factor-factor VIII (MFG-E8) functions as a bridging molecule to promote the removal of dying cells by professional phagocytes. Since MFG-E8 promotes clearance of apoptotic cells, we have explored its therapeutic potential in various organ injury conditions. To develop human MFG-E8 as a potential therapy, we have generated a human cell-expressed, and thus glycosylated, tag-free recombinant human (rh) MFG-E8 and tested its safety and biological activity in vitro. We hypothesize that the tag-free glycosylated rhMFG-E8 is protective in I/R-induced AKI and it can be developed as an effective therapy for AKI. ⋯ Our new human cell-expressed tag-free rhMFG-E8 is protective in I/R-induced AKI and it may have the potential to be further developed as a safe and effective therapy for AKI.
-
Ischemia-reperfusion injury (IRI) often stems from an imbalance between mitochondrial dynamics and autophagy. Melatonin mitigates IRI by regulating mitochondrial dynamics. However, the precise molecular mechanism underlying the role of melatonin in reducing IRI through modulating mitochondrial dynamics remains elusive. ⋯ IRI led to a decline in P-AMPK levels, whereas melatonin pre-treatment increased the level of P-AMPK levels. Silencing AMPK with small interfering RNA exacerbated mitochondrial damage, and in this context, melatonin pre-treatment did not alleviate mitochondrial fission or autophagy levels but resulted in sustained oxidative stress damage. Collectively, these findings indicate that melatonin pre-treatment shields the kidneys from IRI by mitigating excessive mitochondrial fission, moderating autophagy levels, and preserving appropriate mitochondrial fission, all in an AMPK-dependent manner.
-
This study aimed to explore the impact of heat stress (HS) on glutamate transmission-dependent expression levels of interleukin-1β (IL-1β) and IL-18 in BV-2 microglial cells. ⋯ The findings confirmed that microglia could be involved in HS primarily through glutamate metabolisms, influencing the expression levels and release of IL-1β and IL-18.
-
This study aimed to develop and validate a model for prediction of septic shock in neonates with sepsis. ⋯ A predictive model for early diagnosis of septic shock in neonates was developed and initially validated in this study, allowing for timely intervention.
-
Hemorrhagic shock is a major source of morbidity and mortality worldwide. While whole blood or blood product transfusion is a first line treatment, maintaining robust supplies presents significant logistical challenges, particularly in autere environments. OMX is a novel non-hemoglobin (Hb)-based oxygen carrier derived from the H-NOX (Heme-Nitric Oxide/Oxygen binding) protein family. ⋯ We found that OMX was well-tolerated and significantly improved lactate and base deficit trends, and hemodynamic indices (p < 0.05). Median survival time was greater in the OMX-treated group (4.7 vs. 6.0 hr., p < 0.003), and overall survival was significantly increased in the OMX-treated group (25% vs. 85%, p = 0.004). We conclude that OMX is well-tolerated and improves metabolic, hemodynamic and survival outcomes in an ovine model of controlled hemorrhagic shock.