A Heterozygous Phospholamban Variant (p.R14del) Leads to Left Ventricular Involvement and Heart Failure Phenotypes in Arrhythmogenic Right Ventricular Cardiomyopathy.

This study aimed to determine the prevalence and clinical features of Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) caused by pathogenic mutations in the Phospholamban (PLN) gene. The study included 170 patients who had a confirmed diagnosis of ARVC and underwent PLN genetic screening using next-generation sequencing. The findings of this study provide valuable insights into the association between PLN mutations and ARVC, which can aid in the development of more effective diagnostic and treatment strategies for ARVC patients. Out of the patients evaluated, six had a rare pathogenic mutation in PLN with the same p.R14del variant. Family screening revealed that heterozygous carriers of p.R14del exhibited a definite ARVC phenotype. In clinical studies, individuals with the p.R14del mutation experienced a similar rate of malignant arrhythmia events as those with classic desmosome mutations. After adjusting for covariates, individuals with PLN mutations had a two point one seven times greater likelihood of experiencing transplant-related risks compared to those who did not possess PLN mutations (95% CI 1.08-6.82, p = 0.035). The accumulation of left ventricular fat and fibers is a pathological marker for ARVC patients with p.R14del mutations. In a cohort of 170 Chinese ARVC patients, three point five percent of probands had the PLN pathogenic variant (p.R14del) and all were female. Our data shows that PLN-related ARVC patients are at high risk for ventricular arrhythmias and heart failure, which requires clinical differentiation from classic ARVC. Furthermore, carrying the p.R14del mutation can be an independent prognostic risk factor in ARVC patients. Supplementary Information: The online version contains supplementary material available at 10.1007/s43657-023-00126-w.

A single-cell atlas of lung homeostasis reveals dynamic changes during development and aging.

Aging is a global challenge, marked in the lungs by function decline and structural disorders, which affects the health of the elderly population. To explore anti-aging strategies, we develop a dynamic atlas covering 45 cell types in human lungs, spanning from embryonic development to aging. We aim to apply the discoveries of lung's development to address aging-related issues. We observe that both epithelial and immune cells undergo a process of acquisition and loss of essential function as they transition from development to aging. During aging, we identify cellular phenotypic alternations that result in reduced pulmonary compliance and compromised immune homeostasis. Furthermore, we find a distinctive expression pattern of the ferritin light chain (FTL) gene, which increases during development but decreases in various types of lung cells during the aging process.

Ruxolitinib attenuates acute rejection and can serve as an immune induction therapy in heart transplantation.

The benefits of IL2RA antagonists in heart transplant patients are controversial. We aimed to elucidate the effects of IL2RA antagonists and identify targets that could be better than IL2RA antagonists. By using single-cell RNA sequencing of immune cells at different time points in patients receiving IL2RA antagonists, we identified nineteen types of cells. We revealed higher IL2RA expression in regulatory T cells (Tregs), suggesting that IL2RA antagonists attenuated IL-2-induced Treg activation. CD4_C04_IFNGR1 and CD8_C05_IFITM2 which had more cytotoxic effects, remained elevated at later time points. IFNGR1 was upregulated in these two subtypes, but was not expressed in Treg. Ruxolitinib targeted the pathways of IFNGR1 (JAK1/2) while not affecting the pathway of IL-2-induced Tregs activation (JAK3). Ruxolitinib showed prolonged survival compared to IL2RA mAb-treated mice. Our study provided dynamic changes of immune cells after IL2RA antagonists treatment at single-cell resolution. Ruxolitinib has potential as a new immunoinduction therapy without affecting Treg.

Association between admission prothrombin time activity and hospital readmission in heart failure: A retrospective study.

BACKGROUND: Coagulopathy is a common complication of heart failure (HF), but the prognostic significance of coagulation abnormalities for HF is still poorly understood. This investigation sought to elucidate the association between admission prothrombin time activity (PTA) and short-term readmission in HF. METHODS: In this retrospective study, we extracted data from a publicly accessible database for hospitalized HF patients in China. The admission laboratory findings were screened by the least absolute shrinkage and selection operator (LASSO) regression. Afterward, the study population was stratified according to the admission PTA level. In univariate and multivariate analysis, we employed logistics regression model to evaluate the association of admission PTA level with short-term readmission. Subgroup analysis was preformed to examine the interaction effect between admission PTA level and covariates, including age, sex, and systolic blood pressure (SBP). RESULTS: A total of 1505 HF patients were included, of whom 58.7% were female and 35.6% were between 70 and 79 y. In LASSO procedure, admission PTA level was included in optimized models for short-term readmission, and readmitted patients tended to have a lower admission PTA level. Multivariate analysis suggested that the low admission PTA level (admission PTA ≤ 62.3%) was associated with increased risk of 90-day readmission (odds ratio 1.63 [95% CI, 1.09 to 2.46]; P = 0.02) and 180-day readmission (odds ratio 1.65 [95% CI, 1.18 to 2.33]; P = 0.01) compared with patients with the highest admission PTA level (admission PTA ≥ 76.8%) after full adjustment. Moreover, no significant interaction effect was observed in the subgroup analysis, except for admission SBP. CONCLUSION: Low admission PTA level is associated with an increased risk of 90-day and 180-day hospital readmission in patients with HF.

STING regulates the transformation of the proinflammatory macrophage phenotype by HIF1A into autoimmune myocarditis.

Macrophages play an essential role in the pathogenesis of autoimmune myocarditis, but the molecular mechanism remains largely unknown. Here, the role of Stimulator of interferon gene (Sting) in autoimmune myocarditis was investigated. Six-week-old male BALB/c mice received two subcutaneous injections of 250 µg α-MyHC peptide to establish experimental autoimmune myocarditis (EAM). With single-cell RNA sequencing analysis of cardiac immune (Cd45+) cells, Sting was found to initiate proinflammatory macrophage differentiation related to the acute EAM phase. Furthermore, proinflammatory macrophages contribute to the pathogenesis of EAM via hypoxia-inducible factor-1α (Hif1α). A higher expression level of Sting was detected in macrophages from myocarditis, which was positively correlated with Hif1α expression. Single-stranded DNA (ssDNA) accumulation in macrophages in myocarditis was observed in the hearts of EAM mice. Pharmacological blockade of STING by C-176 (a specific inhibitor) ameliorated the inflammatory response of EAM and reduced proinflammatory molecule (Ifn-ß, Tnf-α, Ccl2, and F4/80) expression and Hif1α expression. In vitro studies revealed that ssDNA activated the expression of Sting; in turn, Sting accelerated proinflammatory molecule expression in mouse macrophages. Inhibition of Hif1α expression could reduce Sting-associated cardiac inflammation and proinflammatory molecule expression. In addition, the expression of STING and ssDNA accumulation in macrophages were observed in human autoimmune myocarditis heart samples. STING activated proinflammatory macrophage via HIF1A, promoting the development of autoimmune myocarditis. The STING signaling pathway might provide a novel mechanism of autoimmune myocarditis and serve as a potential therapeutic target for autoimmune myocarditis patients.

Corrigendum: Targeted therapy in cardiovascular disease: A precision therapy era.

[This corrects the article DOI: 10.3389/fphar.2021.623674.].

Effects of different anesthesia methods on postoperative immune function in patients undergoing gastrointestinal tumor resection.

To investigate the effects of different anesthetic methods on postoperative immune function in patients undergoing gastrointestinal tumor resection. Ninety patients undergoing laparoscopic gastrointestinal tumor resection were divided into 3 groups. Patients in the GA group were anesthetized by total intravenous anesthesia. The GE group was anesthetized by general anesthesia combined with epidural anesthesia. The GN group was anesthetized by general anesthesia combined with bilateral Transversus Abdominis Plane block (TAP) and rectus sheath nerve blocks. General anesthesia is total intravenous anesthesia in all three groups. Blood samples were taken to test the changes of peripheral lymphocyte subtype analysis, and levels of plasma cortisol, epinephrine, norepinephrine. Also, the dosage of anesthetic drugs, recovery time, and visual analog scale (VAS) scores were recorded. Postoperative immune indexes, including CD4 count, CD8 count, B, and NK cells, in the GE group were significantly higher than those in NA and GA groups (P < 0.01). Perioperative stress indices, including epinephrine levels, norepinephrine level and aldosterone level, in the GE group were significantly lower than in the GA group and GN group (P < 0.01). The intraoperative/total sufentanil dosage and remifentanil dosage in the GE group were significantly lower than those in the GA and GN groups (P < 0.01). The VAS scores in the GE group were significantly better than those in GA and GN groups (P < 0.01). General anesthesia combined with epidural anesthesia attenuates the increase in inflammatory mediators. Its possible mechanisms include reducing perioperative stress response and reducing perioperative opioid use.

Changes of Plasma Tris(hydroxymethyl)aminomethane and 5-Guanidino-3-methyl-2-oxopentanoic Acid as Biomarkers of Heart Remodeling after Left Ventricular Assist Device Support.

Cardiac function is closely related to heart metabolism. Heart failure patients undergoing LVAD support have shown varying degrees of remodeling of both cardiac function and morphology. However, the metabolic changes in patients with different outcomes are unclear. This study aimed to identify metabolic differences and evaluate metabolomics-based biomarkers in patients with non-improved/improved cardiac function after LVAD support. Sixteen patients were enrolled in this study. Plasma samples were analyzed by using untargeted metabolomic approaches. Multivariate statistical analysis and a Mann-Whitney U-test was performed to clarify the separation in metabolites and to identify changes in plasma metabolites between the two groups, respectively. The efficacy of candidate biomarkers was tested by the area under the curve receiver operating characteristic curve. Using the Metabolomics Standards Initiative level 2, a total of 1542 and 619 metabolites were detected in the positive and negative ion modes, respectively. Enrichment analysis showed that metabolites in improved cardiac function patients were mainly involved in carbohydrate metabolism and amino acid metabolism. Metabolites from non-improved cardiac function patients were mainly involved in hormone metabolism. Furthermore, we found tris(hydroxymethyl)aminomethane and 5-guanidino-3-methyl-2-oxopentanoic acid could serve as biomarkers to predict whether a patient's cardiac function would improve after LVAD support.

N-Acetylcysteine, an ROS Inhibitor, Alleviates the Pathophysiology of Hyperthyroidism-Induced Cardiomyopathy via the ROS/Ca2+ Pathway.

Hyperthyroidism is common and can induce cardiomyopathy, but there is no effective therapeutic strategy. The purpose of this study was to investigate the molecular mechanism of hyperthyroidism-induced cardiomyopathy (HTC) and the effect of N-acetylcysteine (NAC), an ROS inhibitor, on the pathophysiology of HTC in vivo and in vitro. Compared with those in the control groups in vivo and in vitro, TT3 and TT4 were significantly increased, the structure of myocardial cells was enlarged and disordered, and interstitial fibrosis and the apoptosis of myocardial cells were markedly increased in the L-Thy group. The ROS and inflammatory response were increased in the hyperthyroidism group. In the NAC group, the contents of TT3 and TT4 were decreased, the myocardial cell structure was slightly disturbed, fibrosis and apoptosis were significantly reduced, and the ROS level and inflammatory response were significantly reduced. Interestingly, L-Thy decreased the viability of fibroblasts and H9c2 cells, suggesting that L-Thy-induced fibrosis was not caused by the proliferation of fibroblasts. The molecular mechanism of HTC could be explained by the fact that L-Thy could cause cardiac hypertrophy, inflammation, and fibrosis by regulating the Ca2+/calpain/Rcan1-dependent signalling pathway, the Ca2+/Rcan1/NF-κB/p65-dependent signalling pathway, and the Ca2+/ROS/Bcl-2/caspase-3-dependent signalling pathway. In conclusion, NAC can alleviate the pathophysiology of hyperthyroidism-induced cardiomyopathy, probably by regulating the ROS/Ca2+-dependent pathway.

Swelling-Induced Information Camouflage and Optical Decryption on a Transparent Recoverable Hydrogel Surface.

Information camouflage and decryption on hydrogels rely on chemical stimuli such as pH, ultraviolet light, and chemical reactions, in which the cyclability is limited. This work develops a simpler yet effective physical method that can achieve the information camouflage on hydrogels by water swelling and decrypt it under white light. The information camouflage and decryption can proceed with unlimited cycles. To successfully reach the information camouflage, the hydrogel is synthesized with the water swelling ratio in weight as high as 250, which is enabled by the strong electrostatic repulsion of cationic moieties inside the network. At such a high water-swollen state, the hydrogel is still robust and elastic, which provides a mechanical basis to maintain the stability of the camouflaged information. We write information on the hydrogel surface by laser cutting. Upon immersing the hydrogel in water, the high swelling results in huge expansion of the hydrogel, thus inducing the information camouflage. With exposure to white light, the information can be decrypted and becomes visible again. Our protocol utilizes a simple physical process to enable the camouflage and decryption of complex information, which might open an alternative pathway for the development of hydrogel materials in the application of informatics.

Electrochemistry-Induced Improvements of Mechanical Strength, Self-Healing, and Interfacial Adhesion of Hydrogels.

Hydrogels have demonstrated great potential in biomedical and engineering areas. To improve the physical performance, development of efficient physical/chemical protocols is essential. Herein, an electrochemistry functionalization strategy that is capable of enabling the functional improvements of hydrogel is reported. The electrochemistry functionalization is demonstrated on a hydrogel model of polyacrylamide (PAAm)@κ-carrageenan. The electrochemistry reaction generates metal ions (Fe3+ ) that migrate and coordinate with the sulfate groups of κ-carrageenan resulting in the prominent function improvements. In comparison with untreated PAAm@κ-carrageenan hydrogel, it can improve the mechanical strength by 7.37 times, and can increase the interfacial adhesion energy of the hydrogel on a glass surface from 0 to 1400 J m-2 , stronger than the bonding strength of tendons (adhesion energy: ≈800 J m-2 ). Two pieces of hydrogel strips integrate into an intact structure by the electrochemistry functionalization, where the healing efficiency reaches 100% in comparison to the untreated hydrogel. The most significant development is that it enables functional patterning on the hydrogel by the electrode assembly, which provides the hydrogel with modular sensitivity to external pressure. Therefore, it can be a general protocol for rapid generation of multifunctional hydrogels for biomedical and engineering developments.

Targeted Therapy in Cardiovascular Disease: A Precision Therapy Era.

Targeted therapy refers to exploiting the specific therapeutic drugs against the pathogenic molecules (a protein or a gene) or cells. The drug specifically binds to disease-causing molecules or cells without affecting normal tissue, thus enabling personalized and precision treatment. Initially, therapeutic drugs included antibodies and small molecules, (e.g. nucleic acid drugs). With the advancement of the biology technology and immunotherapy, the gene editing and cell editing techniques are utilized for the disease treatment. Currently, targeted therapies applied to treat cardiovascular diseases (CVDs) mainly include protein drugs, gene editing technologies, nucleic acid drugs and cell therapy. Although targeted therapy has demonstrated excellent efficacy in pre-clinical and clinical trials, several limitations need to be recognized and overcome in clinical application, (e.g. off-target events, gene mutations, etc.). This review introduces the mechanisms of different targeted therapies, and mainly describes the targeted therapy applied in the CVDs. Furthermore, we made comparative analysis to clarify the advantages and disadvantages of different targeted therapies. This overview is expected to provide a new concept to the treatment of the CVDs.

Pneumonia scoring systems for severe COVID-19: which one is better.

PURPOSE: To investigate the predictive significance of different pneumonia scoring systems in clinical severity and mortality risk of patients with severe novel coronavirus pneumonia. MATERIALS AND METHODS: A total of 53 cases of severe novel coronavirus pneumonia were confirmed. The APACHE II, MuLBSTA and CURB-65 scores of different treatment methods were calculated, and the predictive power of each score on clinical respiratory support treatment and mortality risk was compared. RESULTS: The APACHE II score showed the largest area under ROC curve in both noninvasive and invasive respiratory support treatment assessments, which is significantly different from that of CURB-65. Further, the MuLBSTA score had the largest area under ROC curve in terms of death risk assessment, which is also significantly different from that of CURB-65; however, no difference was noted with the APACHE II score. CONCLUSION: For patients with COVID, the APACHE II score is an effective predictor of the disease severity and mortality risk. Further, the MuLBSTA score is a good predictor only in terms of mortality risk.

Prognostic value of interleukin-6, C-reactive protein, and procalcitonin in patients with COVID-19.

BACKGROUND: The inflammatory response plays a critical role in coronavirus disease 2019 (COVID-19), and inflammatory cytokine storm increases the severity of COVID-19. OBJECTIVE: To investigate the ability of interleukin-6 (IL-6), C-reactive protein (CRP), and procalcitonin (PCT) to predict mild and severe cases of COVID-19. STUDY DESIGN: This retrospective cohort study included 140 patients diagnosed with COVID-19 from January 18, 2020, to March 12, 2020. The study population was divided into two groups according to disease severity: a mild group (MG) (n = 107) and a severe group (SG) (n = 33). Data on demographic characteristics, baseline clinical characteristics, and the levels of IL-6, CRP, and PCT on admission were collected. RESULTS: Among the 140 patients, the levels of IL-6, CRP, and PCT increased in 95 (67.9 %), 91 (65.0 %), and 8 (5.7 %) patients on admission, respectively. The proportion of patients with increased IL-6, CRP, and PCT levels was significantly higher in the SG than in the MG. Cox proportional hazard model showed that IL-6 and CRP could be used as independent factors to predict the severity of COVID-19. Furthermore, patients with IL-6 > 32.1 pg/mL or CRP > 41.8 mg/L were more likely to have severe complications. CONCLUSION: The serum levels of IL-6 and CRP can effectively assess disease severity and predict outcome in patients with COVID-19.

Publisher Correction: Acetate attenuates inflammasome activation through GPR43-mediated Ca2+-dependent NLRP3 ubiquitination.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Acetate attenuates inflammasome activation through GPR43-mediated Ca2+-dependent NLRP3 ubiquitination.

Acetate has been indicated to be elevated and to regulate inflammation in inflammatory and metabolic diseases. The inflammasome serves as a key component of immune homeostasis, and its dysregulation can lead to various inflammatory disorders. However, little is known about the effects of acetate on inflammasome activation and the underlying mechanism. Here, we demonstrate that acetate attenuates inflammasome activation via GPR43 in a Ca2+-dependent manner. Through binding to GPR43, acetate activates the Gq/11 subunit and subsequent phospholipase C-IP3 signaling to decrease Ca2+ mobilization. In addition, acetate activates soluble adenylyl cyclase (sAC), promotes NLRP3 inflammasome ubiquitination by PKA, and ultimately induces NLRP3 degradation through autophagy. In vivo, acetate protects mice from NLRP3 inflammasome-dependent peritonitis and LPS-induced endotoxemia. Collectively, our research demonstrates that acetate regulates the NLRP3 inflammasome via GPR43 and Ca2+-dependent mechanisms, which reveals the mechanism of metabolite-mediated NLRP3 inflammasome attenuation and highlights acetate as a possible therapeutic strategy for NLRP3 inflammasome-related diseases.

Intraperitoneal Injection of Acetate Protects Mice Against Lipopolysaccharide (LPS)­Induced Acute Lung Injury Through Its Anti-Inflammatory and Anti-Oxidative Ability.

BACKGROUND As a member of short-chain fatty acids, acetate exhibits anti-inflammatory capacity. The present study aimed to investigate the effect of acetate on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and explored its underlying mechanism. MATERIAL AND METHODS Acetate (250 mM, 400 µL) was given intraperitoneally 30 minutes after LPS (5 mg/kg) intratracheal injection. Lung tissues and bronchoalveolar lavage fluid (BALF) were collected 6 hours after the challenge of LPS. The histopathology scores, wet-to-dry weight ratios, protein content, and cytokine levels in BALF were assessed. RESULTS The acetate treatment resulted in improved lung pathological score, alleviated LPS-induced microvascular permeability, and suppressed the production of reactive oxygen species. Furthermore, acetate decreased the level of pro-inflammatory cytokines and chemokines in the lungs and BALF, consistent with the declined immune cell counting found in BALF. In addition, phosphorylation levels of mitogen-activated protein kinase (MAPK) pathway in lung tissues were downregulated by acetate. CONCLUSIONS These results suggested that acetate exerts its protective effects via anti-inflammatory and anti-oxidant activities on LPS-induced ALI.

Fabrication of Cellulose-Nanocrystal-Based Folate Targeted Nanomedicine via Layer-by-Layer Assembly with Lysosomal pH-Controlled Drug Release into the Nucleus.

To increase the cellular uptake and drug loading of cellulose nanocrystal (CNC)-based nanomedicines, folate/ cis-aconityl-doxorubicin@polyethylenimine@CNC (FA/CAD@PEI@CNC) nanomedicines were built up by the building blocks of folate (FA), cis-aconityl-doxorubicin (CAD), polyethylenimine (PEI), and CNCs via the robust layer-by-layer (LbL) assembly technique. The drug loading content (DLC) of FA/CAD@PEI@CNC hybrids was 11.3 wt %, which was almost 20-fold higher than that of the CNC-based nano-prodrug we reported previously. FA/CAD@PEI@CNC nanomedicines showed lysosomal pH-controlled drug release profiles over 24 h. In detail, the cumulative drug release was over 95% at pH 5.5, while the cumulative drug release was only 17% at pH 7.4. In vitro, FA/CAD@PEI@CNC hybrid nanomedicines had a higher (9.7-fold) mean fluorescent intensity (MFI) than that of DOX·HCl, with enhanced cytotoxicity and decreased IC50 against MCF-7. Thus, FA/CAD@PEI@CNC hybrid nanomedicines displayed efficient targetability and enhanced cellular uptake. In addition, FA/CAD@PEI@CNC nanomedicine could deliver more DOX to the nucleus than the control group, due to the ß-carboxylic acid catalyzed breakage of the pH-labile cis-aconityl amide linkages in CAD. These results indicated that FA/CAD@PEI@CNC nanomedicines achieved lysosomal pH-controlled drug release into the nucleus and showed great potential to be high-performance nanomedicines to improve the delivery efficiency and therapy efficacy. This study for CNC-based nanomedicines provided important insights into the bioapplication of CNCs modified by LbL assembly.

Synthesis and Comparative Biological Properties of Ag-PEG Nanoparticles with Tunable Morphologies from Janus to Multi-Core Shell Structure.

Silver nanoparticles synthesized with polymers as coating agents is an effective method to overcome their poor stability and aggregation in solution. Silver-polyethylene glycol (Ag-PEG) nanoparticles were synthesized with the thiol-functionalized polyethylene glycol (SH-PEA) as the coating, reducing and stabilizing agent. The UV irradiation time, polymer and silver nitrate concentration for the synthesis were investigated. The concentration of silver nitrate had significant effect on the morphology of Ag-PEG nanoparticles. When increasing the concentration of silver nitrate, SEM and TEM images showed that Ag-PEG nanoparticles changed from Janus to multi-core shell structure. Meanwhile, pure silver particles in the two hybrid nanoparticles presented spherical shape and had the similar size of 15 nm. The antibacterial activities and cytotoxicity of the two structural Ag-PEG nanoparticles were investigated to understand colloid morphology effect on the properties of AgNPs. The results of antibacterial activities showed that the two structural Ag-PEG nanoparticles exhibited strong antibacterial activities against Staphylococcus aureus, Escherichia coli and Bacillus subtilis. The Janus nanoparticles had larger minimal inhibitory concentration (MIC) and minimum bacterial concentration (MBC) values than the multi-core shell counterparts. The results of cytotoxicity showed the Janus Ag-PEG nanoparticles had lower toxicity than the multi-core shell nanoparticles.

Ouabain Protects Mice Against Lipopolysaccharide-Induced Acute Lung Injury.

BACKGROUND Ouabain, an inhibitor of Na+/K+-ATPase, is a type of endogenous hormone synthesized in the adrenal cortex and hypothalamus. Previous studies found that ouabain potently inhibited inflammatory reactions and regulated immunological processes. Our present study aimed to investigate the therapeutic role of ouabain on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. MATERIAL AND METHODS Ouabain (0.1 mg/kg) or vehicles were intraperitoneally injected into male C57BL/6J mice once a day for 3 consecutive days. One hour after the last injection of ouabain, LPS (5 mg/kg) was administrated through intranasal instillation to induce ALI. 6 hours and 24 hours later, bronchoalveolar lavage fluid (BALF) and lung tissues were harvested to detect the protective effects of ouabain, including protein concentration, inflammation cell counts, lung wet-to-dry ratio, and lung damage. RESULTS The results showed that ouabain attenuated LPS-induced ALI in mice, which was indicated by alleviated pathological changes, downregulated TNF-α, IL-1ß, and IL-6 production, inhibited neutrophils infiltration and macrophages, and ameliorated pulmonary edema and permeability. Further results found the activation of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways were suppressed by ouabain in LPS-induced ALI. CONCLUSIONS These results suggest that ouabain negatively modulates the severity of LPS-induced ALI.