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
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Nonalcoholic fatty liver disease (NAFLD) is a prevalent liver disorder with significant health implications. N6-methyladenosine (m6A) methyltransferase is known to exert regulatory functions in liver-related diseases. This study investigates the intricate role of RNA binding motif protein 15 (RBM15) in modulating inflammation and oxidative stress in NAFLD. ⋯ RNF5 knockdown or ROCK1 overexpression accelerated inflammation and oxidative stress in NAFLD. Taken together, RBM15 upregulated RNF5 expression through m6A methylation modification. RNF5 inhibited ROCK1 expression through ubiquitination modification to mitigate NAFLD.
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Meta Analysis
Protective role of melatonin for acute kidney injury: A systematic review and meta-analysis.
Introduction : Acute kidney injury (AKI) is an important clinical issue that arouses global concerns, which puzzles clinicians and lacks effective drug treatment for AKI until the present. Melatonin has been well recognized to modulate the sleep-wake cycle and had the renal protective effect. However, there are still few clinical trials investigating the relationship between melatonin and AKI. ⋯ Melatonin tended to reduce the serum creatinine and urea nitrogen levels, but there was no statistical significance. Conclusions : Melatonin can increase the estimated glomerular filtration rate and effectively inhibit the occurrence of AKI. More well-designed randomized controlled trials are needed to verify the protective effect of melatonin in the future.
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Sepsis is defined as a life-threatening organ dysfunction caused by excessive host response to infection, and represents the most common cause of in-hospital deaths. Sepsis accounts for 30% of all critically ill patients in the intensive care unit (ICU), and has a global mortality rate of 20%. ⋯ Von Willebrand factor (VWF) and ADAMTS13 are two important regulators of blood coagulation that may be important links between sepsis and mortality in the ICU. Herein we review our current understanding of VWF and ADAMTS13 in sepsis and other critical illnesses and discuss their contribution to disease pathophysiology, their use as markers of severe illness, and potential targets for new therapeutic development.
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Extracellular vesicles (EVs) are a new revelation in cross-kingdom communication, with increasing evidence showing the diverse roles of bacterial EVs (BEVs) in mammalian cells and host-microbe interactions. Bacterial EVs include outer membrane vesicles released by gram-negative bacteria and membrane vesicles generated from gram-positive bacteria. Recently, BEVs have drawn attention for their potential as biomarkers and therapeutic tools because they are nano-sized and can deliver bacterial cargo into host cells. ⋯ Next, the mechanisms and pathways identified by BEVs that stimulate either proinflammatory or anti-inflammatory responses are highlighted. In addition, we discuss the mechanisms by which BEVs regulate host-microbe interactions and their effects on the immune system. Finally, this review focuses on the contribution of BEVs to the pathogenesis of sepsis/septic shock and their therapeutic potential for the treatment of sepsis.
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Randomized Controlled Trial
Prolonged mechanical ventilation in acute respiratory distress syndrome.
Purpose: Trajectory of acute respiratory distress syndrome (ARDS) spans from rapidly improving cases to cases receiving prolonged mechanical ventilation (PMV). We attempted to estimate temporal trends of prevalence and mortality of PMV and to identify risk factors associated with mortality of patients with ARDS receiving PMV. Methods: We performed a secondary analysis of individual patient data from six randomized controlled clinical trials conducted by the ARDS Network. ⋯ Ninety-day mortality of patients receiving PMV did not change over time ( R2 = 0.271, P = 0.290) and remained as high as 36.8%. Ιn the three most recent trials, risk factors associated with mortality among the 250 patients with ARDS receiving PMV included age, malignancy, pneumonia as the cause of ARDS, coagulation dysfunction, and hepatic dysfunction during the first 21 days after trial enrollment. Conclusion: Although prevalence of PMV among patients enrolled in ARDS Network trials gradually declined, mortality did not change. Risk factors associated with mortality were mostly nonmodifiable.