Background Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) induces uncontrolled and self-amplified pulmonary inflammation, and has high morbidity and mortality rates in critically ill patients. In recent years, many bioactive ingredients extracted from herbs have been reported to effectively ameliorate ALI/ARDS via different mechanisms. Ferroptosis, categorized as regulated necrosis, is more immunogenic than apoptosis and contributes to the progression of ALI. In this study, we examined the impact of panaxydol (PX), isolated from the roots of Panax ginseng, on lipopolysaccharide (LPS)-induced ALI in mice. Methods In vivo, the role of PX on LPS-induced ALI in mice was tested by determination of LPS-induced pulmonary inflammation, pulmonary edema and ferroptosis. In vitro, BEAS-2B cells were used to investigate the molecular mechanisms by which PX functions via determination of inflammation, ferroptosis and their relationship. Results Administration of PX protected mice against LPS-induced ALI, including significantly ameliorated lung pathological changes, and decreased the extent of lung edema, inflammation, and ferroptosis. In vitro, PX inhibited LPS-induced ferroptosis and inflammation in bronchial epithelial cell line BEAS-2B cells. The relationship between ferroptosis and inflammation was investigated. The results showed that ferroptosis mediated inflammation in LPS-treated BEAS-2B cells, and PX might ameliorate LPS-induced inflammation via inhibiting ferroptosis. Meanwhile, PX could upregulate Keap1-Nrf2/HO-1 pathway, and selective inhibition of Keap1-Nrf2/HO-1 pathway significantly abolished the anti-ferroptotic and anti-inflammatory functions of PX in LPS-treated cells. Conclusion PX attenuates ferroptosis against LPS-induced ALI via Keap1-Nrf2/HO-1 pathway, and is a promising novel therapeutic candidate for ALI.
Cerebral ischemia caused early neuronal death due to necrosis, followed by delayed neuronal death due to apoptosis. Consequently, autophagy might be involved in all processes of ischemia. HBO could protect the brain against ischemic injury, and the possible mechanisms might be correlated with decreased autophagy activity and decreased apoptosis and necrosis levels.
Introduction and objectives:The goal of this study is to determine whether the application of semi-solid nutrients could increase the efficiency of the enteral nutrition (EN), which was measured daily by administered volume of nutrition/prescribed volume of nutrition.Methods:A total of 28 subjects were finally enrolled in the study and randomized to receive either intermittent feeding (IF) or intermittent feeding with semi-solid nutrients (IS). Three major parameters concerning EN were evaluated in this study: the daily dosage prescribed by doctor, the actual dosage received by subjects, and the acute complications such as diarrhea, vomiting, regurgitation, bowel distension, and lung infection.Results:There were no statistical differences in NRS-2002, and acute gastrointestinal injury between both groups. The IS group (0.98 ± 0.06, P < .01) could receive higher percentage of daily prescribed calories compared to IF (0.73 ± 0.15). The total caloric intake during the first 3 days was higher in IS (2589.29 ± 844.02 vs. 1685.71 ± 388.00, P < .01). The incidence of feeding intolerance (FI) was lower in the IS group (2/14) compared with IF (8/14). However, semi-solid nutrients did not decrease the length of stay, lung infection, or 30-day mortality. Similarly, there was no difference in glycemic variability and stress hyperglycemia.Conclusions:In our cohort of critically ill subjects, the efficiency of the EN was increased by IS, which might be related to the improvement of FI (NCT03017079).
Background: Refeeding syndrome (RFS) is a group of metabolic disorders associated with refeeding after starvation. However, the diagnostic criteria of RFS are highly heterogeneous. This study aimed to identify the best diagnostic criteria of RFS in critically ill patients.Methods: A multicenter, parallel, prospective trial enrolled patients (≥18 years) with mechanical ventilation for more than 3 days. RFS, defined as new-onset hypophosphatemia (<0.87mmol/L) within 72h after feeding and a decreased concentration of serum phosphate of more than 30%, from four hospital ICU of Zhejiang provinces in China. The primary endpoint was the 28-day mortality. Results: Between May 1, 2019 and April 30, 2020, 312 patients were enrolled. Of these, 302 patients were included and completed the trial. Except for APACHE II, there were no significant differences in age, gender, admission type, diagnosis, furosemide application, and hormone application. In the RFS2 and RFS3 groups, the APACHE II score was significantly higher than the non-RFS group (p=0.009 and p=0.01, respectively). In the nutritional baseline data, there were no significant differences between the groups in the PNI index, time to start of nutrition treatment, percentage of start nutrition within 48 hours, parenteral nutrition, feeding intolerance, and caloric intake and protein intake within first week. The NRS2002 score in group 2 and 3 was higher than the non-RFS group (p<0.001 and p=0.001, respectively). Moreover, the BMI index in group 3 was lower than the non-RFS group(p=0.001). Furthermore, the 28-day mortality increased in group 2 compared with the non-RFS group. The length of hospital stay in group 3 was significantly longer than that in the non-RFS group (p=0.008). More importantly, according to the preliminary RFS2 screening criteria, patients were further divided into patients with modified RFS and modified non-RFS. The nosocomial infection rate and 28- or 90-day mortality in the modified RFS group were higher than those of the modified non-RFS group (p=0.006 and p=0.02, respectively).Conclusions: The optimal criterion of RFS was a decrease in serum phosphate level of 0.65mmol/L and below, and a reduction of greater than 0.16 mmol/L within 72 h after starting nutritional support. Trial registration: ClinicalTrials.gov database, NCT04005300. Registered 1 July 2019, https://clinicaltrials.gov/ct2/show/ NCT04005300
Background: Myocardial injury induced by refeeding syndrome (RFS) is one of the important causes of deterioration in critically ill patients. Sirtuin-3 (SIRT3) has been shown to regulate mitochondrial autophagy in myocardial ischemia/reperfusion injury; however, the role of mitochondrial autophagy on RFS-related myocardial injury in patients in critical condition has not been reported on.Methods: Thirty Sprague-Dawley (SD) rats were divided into 3 groups (n=10 each group): the control group; the standard calorie refeeding (SCR) group; and the low calorie refeeding (LCR) group. The rats were weighed every third or four days from day 1 to day 14. On day 14, all rats were anesthetized and received an echocardiography test. Blood and bronchoalveolar lavage fluid (BALF) were collected and tested for arterial oxygen pressure (PaO 2 ), phosphorus (P), and calcium (Ca), creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), and cardiac troponin 1 (cTnI), myeloperoxidase (MPO), tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and IL-6. The histopathological change of hearts and lungs were evaluated, and lung injury score was calculated. Mitochondrial autophagy related proteins (including Beclin1, LC3, mitofusin-2, Mfn2, PINK1, Parkin, and SIRT3) were analyzed using a Western blot. To evaluate the effect of SIRT3, 20 rats were divided into 2 groups (n=10 each group): The adeno-associated virus 9 (AAV9-Nc) group; and the AAV9-SIRT3 overexpression (AAV9-SIRT3) group. The protocols for rats were the same as the SCR group since day 22 after injection of AAV9. The protein expressions of PINK1, Parkin, and SIRT3 were compared between the AAV9-Nc group and AAV9-SIRT3 group.Results: SCR caused significant decline in cardiac contractility and increased inflammatory cell infiltration in myocardial tissue. Meanwhile, Beclin1, LC3, PINK1, Parkin, and SIRT3 levels decreased, while Mfn2 showed no significant change. Furthermore, significant positive correlations were also found between SIRT3 and P, PINK1, and Parkin, and significant negative correlations were found between SIRT3 and CK-MB, LDH, and cTnI. Overexpression of SIRT3 activated the PINK1/Parkin mediated mitochondrial autophagy.Conclusions: SIRT3 has an essential role in RFS-related myocardial injury during LPS induced chronic sepsis in rats, probably via regulating mitochondrial autophagy.
Background: Refeeding syndrome (RFS) was a group of metabolic disorders associated with refeeding after starvation. However, RFS is underdiagnosed in China due to the highly heterogeneous diagnostic criteria. This study was to evaluate the diagnosis of RFS in our intensive care unit (ICU).Methods: Patients monitoring serum phosphate and accepting nutritional treatment more than 3 days were included in our retrospective study. RFS was defined as the new onset hypophosphatemia (<0.87mmol/l) within 72 h after feeding and serum phosphate concentration decreased more than the extent 30%. According to the lowest serum phosphate level within the first 3 days after feeding, all RFS patients were divided into the three groups: Group 1(between 0.65 and 0.87mmol/L as well as more than 30% decrease from baseline), Group 2 (between 0.32 and 0.65mmol/L as well as at least 0.16mmol/L decrease from baseline ) and Group 3 (lower than 0.32mmol/L). The nutritional and prognostic indices were recorded and analyzed within the three groups.Results: A total of 1678 patients were included, of which 150(8.7%) were regularly monitored for serum phosphate. Among these 150 patients, 27 patients were diagnosed the RFS finally. Except for NRS 2002, there were no significant difference in nutritional index such as BMI, percentage of High-risk RFS, total caloric intake, baseline of potassium, magnesium, phosphate and calcium and time to start feeding among three groups. Also, there were no significant differences in clinical outcome, duration of mechanical ventilation and LOS of ICU and hospital. The NRS2002 scores of the three groups were 0.75±0.957, 3.00±1.541 and 4.50±1.049 respectively, and the higher the decline of serum phosphate, the higher the NRS2002 score was (P=0.001). Conclusions: The refeeding hypophosphatemia incidence was not rare in intensive care unit,even serum phosphate has not been monitored regularly. The higher score of NRS2002 might be correlated with greater decline of serum phosphate. However, changes in serum phosphate may be unrelated to prognosis and not be an optimal indicator of low calorie feeding.Trial registration: ClinicalTrials.gov database, NCT04005300. Registered 1 July 2019, https://clinicaltrials.gov/ct2/show/ NCT04005300
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