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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Myeloid-derived suppressor cells (MDSCs) are a heterogenous population of immature myeloid cells hallmarked by their potent immunosuppressive function in a vast array of pathologic conditions. MDSCs have recently been shown to exhibit marked expansion in acute inflammatory states including traumatic injury, burn, and sepsis. Although MDSCs have been well characterized in cancer, there are significant gaps in our knowledge of their functionality in trauma and sepsis, and their clinical significance remains unclear. ⋯ Whether MDSCs may serve as the target for novel therapeutics or an important biomarker in trauma and sepsis is yet to be determined. In this review, we will discuss the current understanding of MDSCs within the context of specific traumatic injury types and sepsis. To improve delineation of their functional role, we propose a systemic approach to MDSC analysis including phenotypic standardization, longitudinal analysis, and expansion of clinical research.
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Sepsis is defined as a life-threatening organ dysfunction, caused by a dysregulated host response to an infection and can progress to septic shock, which represents a major challenge in critical care with a high mortality rate. Currently, there is no definitive treatment available for the dysregulated immune response in sepsis. Therefore, a better understanding of the pathophysiological mechanisms may be useful for elucidating the molecular basis of sepsis and may contribute to the development of new therapeutic strategies. ⋯ This review addresses the main functionality of CB1 and CB2 in sepsis, which can contribute to a better understanding about the pathophysiology of sepsis. Specifically, we discuss the role of CB1 in the cardiovascular system which is one of the biological systems that are strongly affected by sepsis and septic shock. We are also reviewing the role of CB2 in sepsis, specially CB2 activation, which exerts anti-inflammatory activities with potential benefit in sepsis.
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"Cytokine storm" has been used to implicate increased cytokine levels in the pathogenesis of serious clinical conditions. Similarities with Severe Acute Respiratory Syndrome Coronoavirus-2 (SARS CoV-2) and the 2012 Middle Eastern Respiratory Syndrome led early investigators to suspect a "cytokine storm" resulting in an unregulated inflammatory response associated with the significant morbidity and mortality induced by SARS CoV-2. The threshold of blood cytokines necessary to qualify as a "cytokine storm" has yet to be defined. ⋯ The misleading term "cytokine storm" implies increased blood levels of cytokines are responsible for a grave clinical condition. Not all inflammatory conditions resulting in worsened disease states are correlated with significantly elevated cytokine levels, despite an association with the term "cytokine storm". "Cytokine storm" should be removed from the medical lexicon since it does not reflect the mediators driving the disease nor does it predict which diseases will respond to cytokine inhibitors.
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The base excess (BE) parameter can be used as an indicator of mortality. However, study results on the influence of alcohol on the validity of BE as a prognostic parameter in alcohol-intoxicated patients are controversial. Thus, this study examined the hypothesis: An increasing blood alcohol level reduces the prognostic value of the BE parameter on mortality. ⋯ The data demonstrate an existing influence of alcohol on the BE parameter; however, this does not negatively affect the BE as a prognostic parameter at a threshold of ≤ -6 mmol/L.
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After cardiac arrest (CA) and resuscitation, the unfolded protein response (UPR) is activated in various organs including the brain. However, the role of the UPR in CA outcome remains largely unknown. One UPR branch involves spliced X-box-binding protein-1 (XBP1s). ⋯ Finally, after confirming that glucosamine can boost O-GlcNAcylation in the aged brain, we subjected aged mice to 8 min CA, and then treated them with glucosamine. We found that glucosamine-treated aged mice performed significantly better in behavioral tests. Together, our data indicate that the XBP1s/O-GlcNAc pathway is a promising target for CA therapy.