Annexin A1 (AnxA1) is an endogenous protein that modulates anti-inflammatory processes, and its therapeutic potential has been reported in a range of inflammatory diseases. The effect of AnxA1 on ischemia-reperfusion (IR)-induced lung injury has not been examined. In this study, isolated, perfused rat lungs were subjected to IR lung injury induced by ischemia for 40 min, followed by reperfusion for 60 min. The rat lungs were randomly treated with vehicle (phosphate-buffered saline), and Ac2-26 (an active N-terminal peptide of AnxA1) with or without an N-formyl peptide receptor (FPR) antagonist N-Boc-Phe-Leu-Phe-Leu-Phe (Boc2). An in vitro study of the effects of Ac2-26 on human alveolar epithelial cells subjected to hypoxia-reoxygenation was also investigated. Administration of Ac2-26 in IR lung injury produced a significant attenuation of lung edema, pro-inflammatory cytokine production recovered in bronchoalveolar lavage fluid, oxidative stress, apoptosis, neutrophil infiltration, and lung tissue injury. Ac2-26 also decreased AnxA1 protein expression, inhibited the activation of nuclear factor-κB and mitogen-activated protein kinase pathways in the injured lung tissue. Finally, treatment with Boc2 abolished the protective action of Ac2-26. The results indicated that Ac2-26 had a protective effect against acute lung injury induced by IR, which may be via the activation of the FPR.

Various animal studies have shown beneficial effects of hypercapnia in lung injury. However, in patients with acute respiratory distress syndrome (ARDS), there is controversial information regarding the effect of hypercapnia on outcomes. The duration of carbon dioxide inhalation may be the key to the protective effect of hypercapnia. We investigated the effect of pre-treatment with inhaled carbon dioxide on lipopolysaccharide (LPS)-induced lung injury in mice. C57BL/6 mice were randomly divided into a control group or an LPS group. Each LPS group received intratracheal LPS (2 mg/kg); the LPS groups were exposed to hypercapnia (5% carbon dioxide) for 10 min or 60 min before LPS. Bronchoalveolar lavage fluid (BALF) and lung tissues were collected to evaluate the degree of lung injury. LPS significantly increased the ratio of lung weight to body weight; concentrations of BALF protein, tumor necrosis factor-α, and CXCL2; protein carbonyls; neutrophil infiltration; and lung injury score. LPS induced the degradation of the inhibitor of nuclear factor-κB-α (IκB-α) and nuclear translocation of NF-κB. LPS increased the surface protein expression of toll-like receptor 4 (TLR4). Pre-treatment with inhaled carbon dioxide for 10 min, but not for 60 min, inhibited LPS-induced pulmonary edema, inflammation, oxidative stress, lung injury, and TLR4 surface expression, and, accordingly, reduced NF-κB signaling. In summary, our data demonstrated that pre-treatment with 10-min carbon dioxide inhalation can ameliorate LPS-induced lung injury. The protective effect may be associated with down-regulation of the surface expression of TLR4 in the lungs.

Background: In the management of major burn wounds, allogeneic skin transplantation is a critical procedure to improve wound repair. Our previous works found that intermittent exposure to carbon dioxide leads to permissive hypercapnia (HCA) and prolongs skin allograft survival. However, the modulatory effects of HCA exposure on the immune system are not well understood. Objectives: Our purpose was to investigate how intermittent exposure to HCA can effectively reduce the immune reaction to allogeneic skin graft rejection. Methods: A fully major histocompatibility complex-incompatible skin transplant from BALB/c to C57BL/6 mice model was utilized. Immune cells from splenic and draining lymph nodes were analyzed by flow cytometry. Serum proinflammatory cytokines were analyzed by ELISA. Results: Serum levels of IFN-γ, IL-2, IL-6, and TNF-α were significantly decreased in the HCA group. Additionally, the percentage of CD8+ cells in draining lymph nodes was significantly lower in HCA than in the control group. Moreover, the generation rate of FoxP3+ regulatory T cells (Tregs) from spleen naïve CD4+ T cells was increased by intermittent exposure to carbon dioxide. The infiltrated neutrophils were also eliminated by HCA. Taken together, we concluded that intermittent hypercapnia exposure could effectively suppress skin rejection by stimulating Treg cell generation and suppressing immune reactions.

A high fiber diet (HFD) and dietary supplementation with acetate have been reported to have beneficial effects in a variety of diseases. We investigated the effects of a HFD and acetate supplementation on the gut microbiota and hyperoxia-induced acute lung injury (HALI) in mice. Mice were fed a control diet, HFD, or acetate supplementation for three weeks, and their gut microbiome composition, lung tissues, and bronchoalveolar lavage fluid (BALF) were examined after exposure to ambient air or hyperoxia. Both the HFD and acetate supplementation modified the gut microbiota community and increased the proportion of acetate-producing bacteria in mice exposed to hyperoxia. The HFD and acetate supplementation also increased the abundance of Bacteroides acidifaciens and reduced gut dysbiosis according to the ratio of Firmicutes to Bacteroidetes. Compared with hyperoxia-exposed mice fed a control diet, both the HFD and acetate supplementation significantly increased the survival time while reducing the severity of pulmonary edema and the concentrations of protein and inflammatory mediators in BALF. Moreover, the HFD and acetate supplementation reduced the production of free radicals, attenuated NF-κB signaling activation, and decreased apoptosis in the lung tissues. Overall, this study indicates that a HFD or acetate supplementation reduces the severity of HALI through alterations in the gut microbiota to exert anti-inflammatory effects.

The authors would like to make a correction to their published paper [1]

Introduction: Deep diving presents significant physiological stress, yet reliable indicators for monitoring autonomic and stress responses remain underdeveloped. This study examined how prior deep diving experience influences autonomic regulation and stress biomarkers during a simulated dive to a depth of 220 feet.Methods: Twenty-eight Navy divers (15 experienced, 13 novice) underwent psychological assessments (perceived stress, anxiety, fear) and salivary biomarker analysis (cortisol, amylase) pre- and post-dive. Heart rate variability (HRV), including linear (rMSSD, HF) and non-linear indices (SD1, SD1/SD2, sample entropy), was measured at four dive stages (pre-dive, bottom, decompression, and post-dive).Results: After adjusting for age and perceived stress, experienced divers exhibited greater post-dive reductions in cortisol (p = 0.015) and amylase (p = 0.022). Additionally, after controlling for age, perceived stress, and respiratory rate, they also demonstrated significantly higher parasympathetic activity (p ≤ 0.001) and greater HRV complexity (sample entropy, p = 0.023) during decompression. No significant differences were found in self-reported psychological stress.Discussion: Diving experience facilitates enhanced autonomic control and stress adaptation. These findings support the use of real-time physiological monitoring and experience-based training protocols to mitigate risk during deep dives.