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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T cell exhaustion is the main cause of sepsis-induced immunosuppression and is associated with the poor prognosis. Nicotinamide adenine dinucleotide (NAD + ) is well known for its anti-aging effect, but its role in sepsis-induced T cell exhaustion remains to be elucidated. In the present study, using a classic septic animal model, we found that the levels of NAD + and its downstream molecule, which is sirtuins 1 (SIRT1), in T cells in sepsis were decreased. ⋯ Nicotinamide ribose also inhibited the regulatory T cells expansion and programmed cell death 1 expression in CD4 + T cells in sepsis. In addition, the bacteria load, organ damage (lung, heart, liver, and kidney), and the mortality of septic mice were reduced after NR supplementation. In summary, these results demonstrate the beneficial effect of NR on sepsis and T cell exhaustion, which is associated with NAD + /SIRT1 pathway.
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Purpose: To evaluate significant risk variables for sepsis incidence and develop a predictive model for rapid screening and diagnosis of sepsis in patients from the emergency department (ED). Methods: Sepsis-related risk variables were screened based on the PIRO (Predisposition, Insult, Response, Organ dysfunction) system. Training (n = 1,272) and external validation (n = 568) datasets were collected from Peking Union Medical College Hospital (PUMCH) and Beijing Tsinghua Changgung Hospital (BTCH), respectively. ⋯ Both calibration curves of EASE in training and external validation datasets were close to the ideal model and were well-calibrated. Conclusions: The EASE model can predict and screen ED-admitted patients with sepsis. It demonstrated superior diagnostic performance and clinical application promise by external validation and in-parallel comparison with the NEWS scoring system.
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Many patients with cardiac arrest (CA) experience severe kidney injury after the return of spontaneous circulation. This study aimed to compare the renal protective effect of conventional cardiopulmonary resuscitation (CCPR), extracorporeal cardiopulmonary resuscitation (ECPR), and ECPR with therapeutic hypothermia (ECPR+T) in a CA rat model. Twenty-four adult male Sprague-Dawley rats were randomly and equally allocated into the sham, CCPR, ECPR, and ECPR+T groups. ⋯ Furthermore, the ECPR and ECPR+T groups had significantly increased B-cell lymphoma 2 and decreased B-cell lymphoma 2-associated X levels compared with the CCPR group. Extracorporeal cardiopulmonary resuscitation and ECPR+T alleviate kidney damage after CA in rats compared with CCPR. Furthermore, ECPR+T had a better renal protective effect.
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As a multifunctional protein, nucleolin can participate in a variety of cellular processes. Nucleolin also has multiple protective effects on heart disease. Previous studies have shown that nucleolin could not only resist oxidative stress damage and inflammatory damage, but also regulate autophagy to play a protective role in cardiac ischemia. ⋯ Finally, we also found that inhibition of autophagy can reduce mitochondrial biogenesis as well as increase apoptosis, which demonstrated the importance of autophagy. Therefore, we can speculate that nucleolin can protect LPS-induced myocardial injury by regulating autophagy, and this protective effect may be mediated by the interaction with PGC-1α, which can positively regulate the ULK1, an autophagy-related protein. Our study provides a new clue for the cardioprotective effect of nucleolin, and may provide new evidence for the treatment of LPS-induced myocardial injury through the regulation of autophagy.
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Background : Overall outcomes for trauma patients have improved over time. However, mortality for postinjury sepsis is unchanged. The use of relevant preclinical studies remains necessary to understand mechanistic changes after injury and sepsis at the cellular and molecular level. ⋯ PT/CS + PNA right and left lung injury scores were worse than PT + PNA ( P < 0.01). Conclusions : Sepsis, with postinjury pneumonia, induced significant systemic inflammation, organ dysfunction following polytrauma and chronic stress. Advanced animal models that replicate the critically ill human condition will help overcome the classic limitations of previous experimental models and enhance their translational value.