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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Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Macrophages play important roles in the inflammatory process of sepsis by secreting chemokines. Chemokine (CC-motif) ligand 2 (CCL-2) is one of the main proinflammatory chemokines secreted by macrophages that plays a critical role in the recruitment of more monocytes and macrophages to the sites of injury in sepsis, but the mechanisms that regulate CCL-2 expression in macrophages during sepsis are still unknown. ⋯ We further confirmed miR-155 regulated SGK3 to increase LPS-induced CCL-2 by using miR-155 mimics and SGK3 overexpression. Thus, our study demonstrates that miR-155 targets SGK3 to increase LPS-induced CCL-2 expression in macrophages, which promotes macrophage chemotaxis and enhances organs injury during endotoxemia. Our study contributed to a better understanding of the mechanisms underlying the inflammatory response during sepsis.
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Sepsis-induced cardiomyopathy ( SIC ) is a distinct form of myocardial injury that disrupts tissue perfusion and stands as the significant cause of mortality among sepsis patients. Currently, effective preventive or treatment strategies for SIC are lacking. YiQiFuMai injection (YQFM), composed of Panax ginseng C. ⋯ Moreover, GPX4 inhibitor could abolish the effects above. In summary, the study highlights the regulatory effect of YQFM in mitigating myocardial injury. It probably achieves this ameliorative effect by enhancing xCT/GPX4 axis and further reducing ferroptosis.
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Glucagon-like peptide 1 (GLP-1) analogs are used to treat type 2 diabetes, and they can regulate insulin secretion, energy homeostasis, inflammation, and immune cell function. This study sought to determine whether the GLP-1 analog liraglutide exerts a beneficial action in an acute lung injury model of pneumonia-induced sepsis. Methods: Wild-type FVB/NJ mice (n = 114) were infected by intratracheal injection with Pseudomonas aeruginosa Xen5 (4 × 10 4 CFU/mouse) or an equal volume (50 μL) of saline (control) with or without a subcutaneous injection of liraglutide (2 mg/kg, 30 min after infection). ⋯ Primary alveolar type II cells pretreated with liraglutide improved SP-A and SP-B expression after LPS exposure ( P < 0.01). Conclusion: Liraglutide attenuates mortality and lung inflammation/injury in pneumonia-induced sepsis. The increased surfactant expression/secretion and anti-inflammatory effects of liraglutide represent potential mechanisms by GLP-1 agonists potentiate host defense and maintain alveolar respiratory function in acute lung injury.
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Aims: We conducted a systemic review and meta-analysis to evaluate the therapeutic efficacy and safety of soluble guanylate cyclase (sGC) stimulators in patients with heart failure with preserved ejection fraction (HFpEF). Methods : We systematically searched PubMed, Embase, and Cochrane Library databases for original randomized controlled trials comparing sGC stimulators with placebo in HFpEF patients. A random-effects model was applied to evaluate the mortality, quality of life, and drug-related adverse events. ⋯ In addition, drug-related adverse events were more common in patients treated with sGC stimulators (RR [95% CI] = 1.63 [1.25-2.14], P < 0.05). Conclusion : Oral sGC stimulators do not significantly improve mortality outcomes, functional capacity, and quality of life in HFpEF patients but are associated with increased drug-related adverse events. Therefore, we should consider using sGC stimulators in HFpEF patients carefully.