Mucus forms the first line of defence of the intestinal mucosa barrier, and mucin is its core component. Glutamine is a vital energy substance for goblet cells; it can promote mucus synthesis and alleviate damage to the intestinal mucus barrier after burn injury, but its mechanism is not fully understood. This study focused on the molecular mechanisms underlying the effects of glutamine on the synthesis and modification of mucin 2 (MUC2) by using animal and cellular models of burn sepsis. We found that anterior gradient-2 (AGR2) plays a key role in the posttranslational modification of MUC2. Oxidative stress induced by burn sepsis enhanced the S-glutathionylation of AGR2, interfered with the processing and modification of MUC2 precursors by AGR2 and blocked the synthesis of mature MUC2. Further studies revealed that NADPH, catalysed by glucose-6-phosphate dehydrogenase (G6PD), is a key molecule in inhibiting oxidative stress and regulating AGR2 activity. Glutamine promotes O-linked N-acetylglucosamine (O-GlcNAc) modification of G6PD via the hexosamine pathway, which facilitates G6PD homodimer formation and increases NADPH synthesis, thereby inhibiting AGR2 S-glutathionylation and promoting MUC2 maturation, ultimately reducing damage to the intestinal mucus barrier after burn sepsis. Overall, we have demonstrated that the central mechanisms of glutamine in promoting MUC2 maturation and maintaining the intestinal mucus barrier are the enhancement of G6PD glycosylation and inhibition of AGR2 S-glutathionylation.

Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. Although fish oil has been used as an immunonutritional preparations for the treatment of sepsis patients, there is still controversy as to whether it is beneficial to them. We systematically reviewed published clinical trial data to evaluate the effectiveness of fish oil-containing nutrition supplementation in sepsis patients. A systematic search was undertaken in PubMed, Embase, Chinese Biomedicine Database, the Cochrane Library and the China Knowledge Resource Integrated Database to obtain clinical controlled trails. RCTs on nutrition therapy containing fish oil among adult sepsis patients were selected for analysis in comparison with routine therapy. Twenty-five published trials were included in the meta-analysis. Fish oil-containing nutrition supplementation reduced the mortality compared with the control group (relative risk (RR) 0.74, I² = 0%). Fish oil also shortened the ICU stay (MD −3.57 days; 95% CI −4.54, −2.59; p0.05). Parenteral nutrition containing fish oil could significantly decrease mortality in sepsis patients while enteral administration could not. Fish oil-containing nutrition supplementation.

There are a very limited number of reports concerning the relationship between pedestrian head injuries and collision parameters through a combination of statistical analysis methods and finite element method (FEM). This study aims to explore the characteristics of pedestrian head injuries in car–pedestrian collisions at different parameters by using the two means above. A retrospective analysis of pedestrian head injuries was performed based on detailed investigation data of 61 car–pedestrian collision cases. The head damage assessment parameters (head injury criterion (HIC), peak stress on the skull, maximal principal strain for the brain) in car–pedestrian simulation experiments with four contact angles and three impact velocities were obtained by FEM. The characteristics of the pedestrian head injuries were discussed by comparing and analyzing the statistical analysis results and finite element analysis results. The statistical analysis results demonstrated a significant difference in skull fractures, contusion and laceration of brain and head injuries on the abbreviated injury scale (AIS)3+ was found at different velocities (p < 0.05) and angles (p < 0.05). The simulation results showed that, in pedestrian head-to-hood impacts, the values of head damage assessment parameters increased with impact velocities. At the same velocity, these values from the impact on the pedestrian’s back were successively greater than on the front or the side. Furthermore, head injury reconstruction and prediction results of two selected cases were consistent with the real injuries. Overall, it was further spelled out that, for shorter stature pedestrians, increased head impact velocity results in greater head injury severity in car–pedestrian collision, especially in pedestrian head-to-hood impacts. Under a back impact, the head has also been found to be at greater damage risk for shorter stature pedestrians, which may have implications on automotive design and pedestrian protection research if prevention and treatment of these injuries is to be prioritized over head injuries under a front or side impact.

Background: Intestinal stem cells (ISCs) play a pivotal role in maintaining intestinal homeostasis and facilitating the restoration of intestinal mucosal barrier integrity. Glutamine (Gln) is a crucial energy substrate in the intestine, promoting the proliferation of ISCs and mitigating damage to the intestinal mucosal barrier after burn injury. However, the underlying mechanism has not yet been fully elucidated. The objective of this study was to explore the mechanism by which Gln facilitates the proliferation of ISCs. Methods: A mouse burn model was established to investigate the impact of Gln on intestinal function. Subsequently, crypts were isolated, and changes in TP53-induced glycolysis and apoptosis regulator (TIGAR) expression were assessed using real-time quantitative polymerase chain reaction (RT-qPCR), western blotting, immunohistochemistry, and immunofluorescence. The effects of TIGAR on cell proliferation were validated through CCK-8, EdU, and clonogenicity assays. Furthermore, the effect of TIGAR on Yes-associated protein (YAP) nuclear translocation and ferroptosis was examined by western blotting and immunofluorescence staining. Finally, dot blot analysis and methylation-specific PCR were performed to evaluate the effect of Gln on TIGAR promoter methylation. Results: The mRNA and protein levels of TIGAR decreased after burn injury, and supplementation with Gln increased the expression of TIGAR. TIGAR accelerates the nuclear translocation of YAP, thereby increasing the proliferation of ISCs. Concurrently, TIGAR promotes the synthesis of nicotinamide adenine dinucleotide phosphate (NADPH) and glutathione to suppress ferroptosis in ISCs. Subsequent investigations demonstrated that Gln inhibits TIGAR promoter methylation by increasing the expression of the demethylase ten-eleven translocation. This change increased TIGAR transcription, increased NADPH synthesis, and reduced oxidative stress, thereby facilitating the restoration of intestinal mucosal barrier integrity post-burn injury. Conclusions: Our data confirmed the inhibitory effect of Gln on TIGAR promoter methylation, which facilitates YAP translocation into the nucleus and suppresses ferroptosis, ultimately promoting the proliferation of ISCs.

Severe burn injury causes a hypermetabolic response, resulting in muscle protein catabolism and multiple organ damage syndrome. However, this response has not yet been continuously characterized by metabolomics in patients. This study aims to quantify temporal changes in the metabolic processes of patients with severe burns. We employed ¹H-nuclear magnetic resonance (NMR) spectroscopy to scrutinize metabolic alterations during the initial 35 days following burn injury in a cohort of 17 adult patients with severe burns, with 10 healthy individuals included as controls. Plasma specimens were collected from patients on postburn days 1, 3, 7, 14, 21, 28 and 35. After performing multivariate statistical analysis, repeated-measures analysis of variance and time-series analysis, we quantified changes in metabolite concentrations. Among the 36 metabolites quantified across 119 samples from burn patients, branched-chain amino acids, glutamate, glycine, glucose, pyruvate, lactate, trimethylamine N-oxide and others exhibited obvious temporal variations in concentration. Notably, these metabolites could be categorized into three clusters based on their temporal characteristics. The initial response to injury was characterized by changes in lactate and amino acids, while later changes were driven by an increase in fatty acid catabolism and microbial metabolism, leading to the accumulation of ketone bodies and microbial metabolites. Metabolomics techniques utilizing NMR have the potential to monitor the intricate processes of metabolism in patients with severe burns. This study confirmed that the third day after burn injury serves as the boundary between the ebb phase and the flow phase. Furthermore, identification of three distinct temporal patterns of metabolites revealed the intrinsic temporal relationships between these metabolites, providing clinical data for optimizing therapeutic strategies.

Background: Enteral nutrition (EN) is an important treatment for burn patients. However, severe gastrointestinal damage caused by major burns often leads to EN intolerance. Trophic EN solves this problem basically, but how to transition from trophic EN to standard EN smoothly is still a challenge in burn clinical nutrition. The aim of this study is to investigate the effects of EN with different energy supplies on metabolic changes, organ damage and prognosis in burned rats.Methods: Different feeding regimens were designed based on the continuous monitoring of resting energy expenditure in rats. Thirty-two Sprague–Dawley rats were randomly divided into a normal control group, burn +50% REE group, burn +75% REE group and burn +100% REE group. At the end of a nutritional treatment cycle (14th day), nuclear magnetic resonance spectroscopy, blood biochemistry analysis and quantification of subscab bacteria were performed to explore the differences in metabolic changes, degrees of organ damage and prognoses between the groups.Results: Sixteen metabolites involving seven metabolic pathways were identified from the different energy supply groups. After burn injury, resting energy consumption and body weight loss increased obviously. Meanwhile, weight loss was inversely related to energy supply. The greatest changes in the degree of organ damage, the level of plasma proteins, lipids and endotoxins, as well as the quantification of subscab bacteria were observed in the 50% REE group, followed by the 75 and 100% groups.Conclusions: Achieving an early balance between energy supply and expenditure is conducive to mitigating metabolic disorders and improving prognosis after burn injury.