Dynamic lymphocyte-CRP ratio as a predictor: a single-centre retrospective study on disease severity and progression in adult COVID-19 patients.

OBJECTIVE: To assess the efficacy of dynamic changes in lymphocyte-C-reactive protein ratio (LCR) on differentiating disease severity and predicting disease progression in adult patients with Coronavirus disease 2019 (COVID-19). METHODS: This single-centre retrospective study enrolled adult COVID-19 patients categorized into moderate, severe and critical groups according to the Diagnosis and Treatment of New Coronavirus Pneumonia (ninth edition). Demographic and clinical data were collected. LCR and sequential organ failure assessment (SOFA) score were calculated. Lymphocyte count and C-reactive protein (CRP) levels were monitored on up to four occasions. Disease severity was determined concurrently with each LCR measurement. RESULTS: This study included 145 patients assigned to moderate (n = 105), severe (n = 33) and critical groups (n = 7). On admission, significant differences were observed among different disease severity groups including age, comorbidities, neutrophil proportion, lymphocyte count and proportion, D-Dimer, albumin, total bilirubin, direct bilirubin, indirect bilirubin, CRP and SOFA score. Dynamic changes in LCR showed significant differences across different disease severity groups at different times, which were significantly inversely correlated with disease severity of COVID-19, with correlation coefficients of -0.564, -0.548, -0.550 and -0.429 at four different times. CONCLUSION: Dynamic changes in LCR can effectively differentiate disease severity and predict disease progression in adult COVID-19 patients.

CircPTP4A2 Promotes Microglia Polarization in Cerebral Ischemic Stroke via miR-20b-5p/YTHDF1/TIMP2 Axis.

Activated microglia play dual roles in ischemic stroke (IS) according to its polarization states. Herein, we investigated the function of circPTP4A2 in regulating microglia polarization in IS. IS models were established by MACO/R and OGD/R treatment. TTC staining was employed to detect cerebral infarct size. Cell vitality was measured using CCK-8 assay. CD16 and CD206 levels were examined using flow cytometry. The interactions between circPTP4A2, miR-20b-5p, and YTHDF1 were analyzed by dual-luciferase reporter gene, RIP, or RNA pull-down assays. circPTP4A2 was upregulated in IS patients. circPTP4A2 knockdown alleviated MCAO/R-induced cerebral injury in mice. circPTP4A2 knockdown promoted microglia M2 polarization after OGD/R. circPTP4A2 promoted YTHDF1 expression by sponging miR-20b-5p. The promoting effect of circPTP4A2 knockdown on microglia M2 polarization was abrogated by miR-20b-5p inhibition. YTHDF1 activated the NF-κB pathway by increasing TIMP2 mRNA stability and expression. circPTP4A2 downregulation promoted microglia M2 polarization to inhibit IS development by regulating the miR-20b-5p/YTHDF1/TIMP2/NF-κB axis.

Continuous Renal Replacement Therapy With oXiris Filter May Not be an Effective Resolution to Alleviate Cytokine Release Syndrome in Non-AKI Patients With Severe and Critical COVID-19.

In this study, we aimed to determine whether continuous renal replacement therapy (CRRT) with oXiris filter may alleviate cytokine release syndrome (CRS) in non-AKI patients with severe and critical coronavirus disease 2019 (COVID-19). A total of 17 non-AKI patients with severe and critical COVID-19 treated between February 14 and March 26, 2020 were included and randomly divided into intervention group and control group according to the random number table. Patients in the intervention group immediately received CRRT with oXiris filter plus conventional treatment, while those in the control group only received conventional treatment. Demographic data were collected and collated at admission. During ICU hospitalization, the concentrations of circulating cytokines and inflammatory chemokines, including IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ, were quantitatively measured daily to reflect the degree of CRS induced by SARS-CoV-2 infection. Clinical data, including the severity of COVID-19 white blood cell count (WBC), neutrophil proportion (NEUT%), lymphocyte count (LYMPH), lymphocyte percentage (LYM%), platelet (PLT), C-reaction protein (CRP), high sensitivity C-reactive protein (hs-CRP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TB), albumin (ALB), serum creatinine (SCr), D-Dimer, fibrinogen (FIB), IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ, number of hospital days and sequential organ failure assessment (SOFA) score were obtained and collated from medical records, and then compared between the two groups. Age, and SCr significantly differed between the two groups. Besides the IL-2 concentration that was significantly lower on day 2 than that on day 1 in the intervention group, and the IL-6 concentrations that were significantly higher on day 1, and day 2 in the intervention group compared to the control group, similar to the IL-10 concentration on day 5, there were no significant differences between the two groups. To sum up, CRRT with oXiris filter may not effectively alleviate CRS in non-AKI patients with severe and critical COVID-19. Thus, its application in these patients should be considered with caution to avoid increasing the unnecessary burden on society and individuals and making the already overwhelmed medical system even more strained (IRB number: IRB-AF/SC-04).

MicroRNA-363-3p/sphingosine-1-phosphate receptor 1 axis inhibits sepsis-induced acute lung injury via the inactivation of nuclear factor kappa-B ligand signaling.

Infection-associated inflammation and coagulation are critical pathologies in sepsis-induced acute lung injury (ALI). This study aimed to investigate the effects of microRNA-363-3p (miR-363-3p) on sepsis-induced ALI and explore the underlying mechanisms. A cecal ligation and puncture-induced septic mouse model was established. The results of this study suggested that miR-363-3p was highly expressed in lung tissues of septic mice. Knockdown of miR-363-3p attenuated sepsis-induced histopathological damage, the inflammation response and oxidative stress in lung tissues. Furthermore, knockdown of miR-363-3p reduced the formation of platelet-derived microparticles and thrombin generation in blood samples of septic mice. Downregulation of miR-363-3p suppressed sphingosine-1-phosphate receptor 1 (S1PR1) expression in lung tissues and subsequently inactivated the nuclear factor kappa-B ligand (NF-κB) signaling. A luciferase reporter assay confirmed that miR-363-3p directly targeted the 3'-untranslated region of the mouse S1pr1 mRNA. Collectively, our study suggests that inactivation of NF-κB signaling is involved in the miR-363-3p/S1PR1 axis-mediated protective effect on septic ALI.

Clinical characteristics and severity of beta and delta variants of SARS-CoV-2 and the effect of vaccine on delta variants.

Background: The Delta variant of concern (VOC) is rapidly becoming the dominant strain globally. We report the clinical characteristics and severity of hospitalized patients infected with Delta and Beta VOCs during the local outbreak in Harbin, Heilongjiang Province, China, and the effect of vaccines on the Delta variant. Methods: We collected a total of 735 COVID-19 patients from the First Affiliated Hospital of Harbin Medical University, including 96 cases infected with the Delta VOC and 639 cases infected with the Beta VOC. Demographic, clinical characteristic and laboratory findings were collected and compared. Results: Differences in viral shedding, IgG and IgM levels, and the neutrophil-to-lymphocyte ratio were noted between the Delta and Beta VOCs (p < 0.05). Survival analysis of the two groups revealed longer viral shedding of the Delta VOC (p < 0.05). For the Delta VOC, the longer the vaccination period, the lower the IgG and IgM levels. IgM levels were higher in the convalescent plasma group, whereas lymphocyte counts were lower. Conclusions: Delta VOC virus shedding was longer compared with Beta VOC shedding. Vaccination with inactivated vaccines can reduce the severe illness rate of the Delta VOC. IgG and IgM levels are reduced as the time period between the first and second vaccine doses increases.

Cytokine levels in sputum, not serum, may be more helpful for indicating the damage in the lung and the prognosis of severe COVID-19 - A case series.

PURPOSE: To describe the relationship between the severity of lung damage and cytokine levels in sputum, bronchoalveolar lavage fluid (BALF), serum. METHOD: Eight severe patients infected with coronavirus disease 2019 (COVID-19) were admitted and their cytokines and chest computed tomography (CT) were analyzed. RESULTS: Compared with in serum, IL-6 and TNF-α in sputum and in BALF show more directly reflect the severity of COVID-19 critical patients. The gradient ratio of IL-6 levels may predict the prognosis of severe patients. CONCLUSION: Cytokine levels in the sputum may be more helpful for indicating lung damage. Local intervention through the respiratory tract is expected to benefit patients with severe COVID-19.

COVID-19 patient with an incubation period of 27 d: A case report.

BACKGROUND: As a highly contagious disease, coronavirus disease 2019 (COVID-19) is wreaking havoc around the world due to continuous spread among close contacts mainly via droplets, aerosols, contaminated hands or surfaces. Therefore, centralized isolation of close contacts and suspected patients is an important measure to prevent the transmission of COVID-19. At present, the quarantine duration in most countries is 14 d due to the fact that the incubation period of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is usually identified as 1-14 d with median estimate of 4-7.5 d. Since COVID-19 patients in the incubation period are also contagious, cases with an incubation period of more than 14 d need to be evaluated. CASE SUMMARY: A 70-year-old male patient was admitted to the Department of Respiratory Medicine of The First Affiliated Hospital of Harbin Medical University on April 5 due to a cough with sputum and shortness of breath. On April 10, the patient was transferred to the Fever Clinic for further treatment due to close contact to one confirmed COVID-19 patient in the same room. During the period from April 10 to May 6, nucleic acid and antibodies to SARS-CoV-2 were tested 7 and 4 times, respectively, all of which were negative. On May 7, the patient developed fever with a maximum temperature of 39℃, and his respiratory difficulties had deteriorated. The results of nucleic acid and antibody detection of SARS-CoV-2 were positive. On May 8, the nucleic acid and antibody detection of SARS-CoV-2 by Heilongjiang Provincial Center for Disease Control were also positive, and the patient was diagnosed with COVID-19 and reported to the Chinese Center for Disease Control and Prevention. CONCLUSION: This case highlights the importance of the SARS-CoV-2 incubation period. Further epidemiological investigations and clinical observations are urgently needed to identify the optimal incubation period of SARS-CoV-2 and formulate rational and evidence-based quarantine policies for COVID-19 accordingly.

Preliminary study of microparticle coagulation properties in septic patients with disseminated intravascular coagulation.

BACKGROUND: Sepsis typically results in enhanced coagulation system activation and microthrombus formation. Microparticle (MP) production promotes coagulation and enhances pro-coagulation. This study investigated how circulating MP levels and tissue factor-bearing MP (TF+-MP) activity caused coagulation in patients with septic disseminated intravascular coagulation (DIC). METHODS: Thirty patients with septic DIC and 30 healthy controls were studied from December 2017 to March 2019. Patient blood samples were collected at enrolment (day 1) and on days 3 and 5; DIC scores and Sequential Organ Failure Assessment (SOFA) scores were recorded. TF+-MP activity was measured using TF-dependent factor Xa generation experiments. Circulating MP concentrations were determined by MP capture assay. Clotting factor activity, antithrombin level, soluble thrombomodulin, and serum tissue factor pathway inhibitor (TFPI) concentrations were measured. RESULTS: Patients with septic DIC had lower circulating MP levels than healthy control patients. Circulating MP levels in patients with septic DIC were positively correlated with DIC scores and negatively correlated with coagulation factors, but TF+-MP activity did not correlate with clotting factor levels and TFPI. CONCLUSIONS: In patients with septic DIC, circulating MP levels are important in promoting coagulation activation and increasing clotting factor consumption. TF+-MP activity may not be the main form of active TF.

Standardization of critical care management of non-critically ill patients with COVID-19.

The large global outbreak of coronavirus disease 2019 (COVID-19) has seriously endangered the health care system in China and globally. The sudden surge of patients with severe acute respiratory syndrome coronavirus 2 infection has revealed the shortage of critical care medicine resources and intensivists. Currently, the management of non-critically ill patients with COVID-19 is performed mostly by non-intensive care unit (ICU) physicians, who lack the required professional knowledge, training, and practice in critical care medicine, especially in terms of continuous monitoring of the respiratory function, intervention, and feedback on treatment effects. This clinical problem needs an urgent solution. Therefore, here, we propose a series of clinical strategies for non-ICU physicians aimed at the standardization of the management of non-critically ill patients with COVID-19 from the perspective of critical care medicine. Isolation management is performed to facilitate the implementation of hierarchical monitoring and intervention to ensure the reasonable distribution of scarce critical care medical resources and intensivists, highlight the key patients, timely detection of disease progression, and early and appropriate intervention and organ function support, and thus improve the prognosis. Different management objectives are also set based on the high-risk factors and the severity of patients with COVID-19. The approaches suggested herein will facilitate the timely detection of disease progression, and thus ensure the provision of early and appropriate intervention and organ function support, which will eventually improve the prognosis.

Decreased T Cell Levels in Critically Ill Coronavirus Patients: Single-Center, Prospective and Observational Study.

BACKGROUND: Since Dec. 2019, the COVID-19 pandemic has been an outbreak. T cells play an important role in dealing with various disease-causing pathogens. However, the role of T cells played in COVID-19 patients is still unknown. Our study aimed to describe the immunologic state of the critically ill COVID-19 patients. METHODS: A total of 63 patients with confirmed COVID-19 pneumonia were admitted to the Department of Intensive Care Unit of the First Affiliated Hospital of Harbin Medical University. The immunologic characteristics (lymphocyte apoptosis, the expression of PD-1 and HLA-DR in T cells, T cell subset levels, redistribution and the production of inflammatory factors) as well as their laboratory parameters were compared between severe group and critical group. RESULTS: The level of T cells in peripheral blood was decreased in critical patients compared with that in severe patients, but the expression levels of PD-1 (CD4+: 24.71% VS 30.56%; CD8+: 33.05% VS 32.38%) and HLA-DR (T cells: 36.28% VS 27.44%; monocytes: 20.58% VS 23.83%) in T cells were not significantly changed, and apoptosis and necrosis were not different in lymphocytes (apoptosis: 1.04% VS 1.27%; necrosis: 0.67% VS 1.11%), granulocytes, or monocytes between those two groups. CONCLUSION: There is severe immunosuppression in critically ill COVID-19 patients. Redistribution of T cells might be the main reason for lymphocytic decline. Decreasing the infiltration of T lymphocytes in the lung may be beneficial for the treatment of COVID-19.

Knockdown CD44 promote the inflammatory response through the autophagy pathway in mouse models of pulmonary contusion.

BACKGROUND: The effects of CD44, via the anti-inflammatory functions of autophagy, on lung injuries following pulmonary contusion (PC) and cell apoptosis were investigated. METHODS: Acute lung injury (ALI) mouse models were established by inducing lung injury via PC. This injury was verified using hematoxylin and eosin (H&E) staining, following which bronchoalveolar lavage fluid (BALF) was collected from these mice for analysis and further experimentation. CD44, LC3 I/II ratio, Beclin-1, and p62 expression levels in A549 cells were determined using immunohistochemistry, and western blot assays. CCK-8, flow cytometry, and acridine orange/ethidium bromide (AO/EB) fluorescence staining were used to quantify cell growth induced by BALF. LC3 II and LC3 I expression was determined through immunofluorescence. CD44-knockdown mice were used to demonstrate lung function after PC. RESULTS: The successful establishment of the ALI mouse models, created via PC was confirmed by an enhanced inflammatory response in the lung tissue, markers of cell autophagy. The ALI mice were found to have elevated CD44 expression. The viability of A549 cells exposed to BALF was downregulated, while the knockdown of CD44 promoted this effect. AO/EB and flow cytometry also indicated that the knockdown of CD44 promoted the cell apoptosis induced by BALF. Western blot analysis showed that knockdown of CD44 can inhibit LC3 I/II, p62, and Beclin-1 expression induced by BALF exposure. Additionally, knockdown of CD44 in mice was found to promote PC-induced lung injury through the attenuation of autophagy. CONCLUSIONS: Knockdown CD44 was shown to inhibit cell growth and induced cell apoptosis via autophagy signaling pathways, promote mice with ALI induced by PC in vivo and in vitro.

Lycorine attenuates lipopolysaccharide-induced acute lung injury through the HMGB1/TLRs/NF-κB pathway.

Lung injury associated with systemic inflammatory response is a common problem affecting human health. Previous studies have shown that lycorine exerts a anti-inflammatory effect. However, whether lycorine alleviates lung injury remains unclear. To explore this issue, BALB/c mice and MLE-12 cells were treated with lipopolysaccharide (LPS) to establish lung injury mouse model and cell model, respectively. Glycyrrhizic acid, known as an inhibitor of ALI, was also used to study the effects of lycorine in vitro. Our results showed that after LPS treatment, the lung injury score, lung wet-to-dry weight ratio, and malondialdehyde (MDA) production in the lung tissues and the expression levels of tumor necrosis factor-α, interleukin-1ß, and interleukin-6 in bronchoalveolar lavage fluid were significantly increased, whereas their levels were decreased by lycorine. Additionally, LPS injection activated the high-mobility group box 1 (HMGB1)/Toll-like receptors (TLRs)/NF-κB pathway. However, lycorine treatment attenuated the activity of the HMGB1/TLRs/NF-κB pathway in the lung tissues. In vitro studies showed that lycorine administration significantly decreased the levels of inflammatory cytokines and MDA and attenuated the activity of the HMGB1/TLRs/NF-κB pathway in LPS-treated cells. Moreover, the inhibitory effects of lycorine on the inflammatory response and oxidative stress in LPS-treated lung cells were similar with that of glycyrrhizic acid, and this inhibition was intensified by both lycorine and glycyrrhizic acid treatment. We suggest that lycorine could alleviate LPS-induced lung injury of inflammation and oxidative stress by blocking the HMGB1/TLRs/NF-κB pathway, which gives a new perspective for ALI therapy to treat lycorine as a potential treatment clinically.

Fibronectin (FN) cooperated with TLR2/TLR4 receptor to promote innate immune responses of macrophages via binding to integrin ß1.

Macrophages could adhere to extracellular matrix molecules(ECM) to induce the expression of pro-inflammatory mediators and phagocytosis that contribute to the pathogenesis of pulmonary infection diseases. Fibronectin (FN) is a large glycoprotein capable of interacting with various ECM molecules produced by a variety of cell types and involved in cell attachment and chemotaxis. However, it is unknown whether FN regulates the expression of pro-inflammatory mediators and phagocytosis of macrophages in the injured lung tissue. Here, we investigated the interaction between FN and integrin ß1 in macrophages, which promotes toll-like receptor 2/4 (TLR2/TLR4) signaling pathways to enhance expression of pro-inflammatory mediators and phagocytosis by macrophages. Our results show that lipopolysaccharide (LPS), lipoteichoic acid (LTA) and peptidoglycan (PGN) significantly increase FN expression of macrophages; FN substantially enhances interleukin 6 (IL-6), tumor necrosis factor-α (TNFα), ras-related C3 botulinum toxin substrate 1/2 (Rac1/2), and cell division control protein 42 homolog (Cdc42) expression and phagocytosis of macrophages. However, FN could not enhance pro-inflammatory cytokines and phagocytosis of macrophages induced by LPS and PGN in integrin ß1-/- macrophages. Furthermore, applied integrin ß1 blocking peptide abrogated the effects that FN promotes innate immune responses of macrophages to LPS and PGN. Those data indicated that the enhanced pro-inflammatory mediators and phagocytosis of macrophages by FN-integrin ß1 signal was through co-operating with TLR2/TLR4 signaling. This study suggests that FN play an essential role in the pathogenesis of pulmonary infection disease.

Efficacy and safety of anti-interleukin-5 therapy in patients with asthma: A pairwise and Bayesian network meta-analysis.

INTRODUCTION: Anti-interleukin-5 therapy has been proposed as a novel and promising treatment option in asthma treatment. However, the optimum monoclonal antibodies for asthma treatment remain uncertain. METHODS: We searched the PubMed, EMBASE and Cochrane databases from their inceptions to June 2018 for randomized controlled trials that reported pulmonary function, adverse events, Asthma Quality of Life Questionnaire (AQLQ) scores, and asthmatic exacerbations resulting from anti-interleukin-5 therapy in asthma patients. Extracted data were analyzed by pairwise and network meta-analysis. RESULTS: Twenty-one randomized studies were identified for this analysis. By pairwise meta-analysis using a placebo as the reference, patients treated with monoclonal antibodies were associated with significantly improved forced expiratory volume (FEV1) values (standard mean difference [SMD], 0.18; 95% confidence interval [CI], 0.12-0.23; P < 0.001), lower rates of adverse events (risk ratio [RR], 0.93; 95% CI, 0.90-0.97; P < 0.001) and significant improvements in the AQLQ scores (SMD, 0.20; 95% CI, 0.13-0.26; P < 0.001). There were no significant differences in exacerbations risks (RR, 0.68; 95% CI, 0.11-4.14; P = 0.097). According to network meta-analysis, adverse events-related benefits were seen only with reslizumab, while AQLQ scores benefits, and pulmonary function benefits were still seen with all three monoclonal antibodies. The assessment of rank probabilities indicated that reslizumab presented the greatest likelihood of having benefits for pulmonary function, reducing adverse events and improving AQLQ scores when compared with the placebo, and mepolizumab presented the best benefits for reducing asthmatic exacerbations. CONCLUSIONS: Anti-interleukin-5 therapy appears to be a safe and effective treatment for asthma patients with respect to pulmonary lung function, adverse events and AQLQ scores, and do not increase asthmatic exacerbations. Our network meta-analysis in patients with asthma suggests that reducing adverse events benefits due to reslizumab, and pulmonary lung function benefits as well as good AQLQ scores are seen with respect to the three antibodies. Network meta-analysis indicates the probability that the best anti-interlukin-5 therapy for asthma patients might be reslizumab, but further trials are required to determine the most effective asthma treatment drug.

Angptl2 deficiency attenuates paraquat (PQ)-induced lung injury in mice by altering inflammation, oxidative stress and fibrosis through NF-κB pathway.

Paraquat (PQ) is one of the most extensively used herbicides, possessing high toxicity for humans and animals. The lung is the main target organ by the poisoning of PQ resulting in acute lung injury. Nonetheless, molecular mechanisms underlying PQ-induced lung injury remain unclear. Here, we ask if angiopoietin-like protein 2 (Angptl2), a pro-inflammatory protein, contributes to inflammation that accelerates acute lung injury. The results indicated that abundant Angptl2 expression was observed in lung tissues of PQ-treated mice. Histological analysis revealed that PQ-induced histological changes were alleviated by Angptl2 knockout (Angptl2-/-). Angptl2-/- in PQ-treated mice attenuated acute lung injury progression by reducing the number of total cells, total leukocytes, neutrophils and macrophages in bronchoalveolar lavage fluid (BALF) and reducing inflammatory response through the inactivation of nuclear factor kappa B (NF-κB) pathway. Angptl2-/- reduced oxidative stress in PQ-treated mice, as evidenced by the enhanced superoxide dismutase (SOD) activity and reduced malondialdehyde (MDA) levels in serum or lung tissue samples, which was accompanied with increased expressions of nuclear respiratory factor 2 (Nrf-2), heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO-1). PQ-induced fibrosis was also improved in Angptl2-/- mice by decreasing pulmonary transforming growth factor (TGF)-ß1 expressions. In vitro, we found that Angptl2 knockdown-suppressed inflammation, oxidative stress and fibrosis was restored by increasing NF-κB activation in PQ-incubated A549 cells; however, the results above were significantly reversed by inactivating NF-κB using its inhibitor, Bay 11-7085 or LY2409881. Therefore, Angptl2 could provide therapeutic effects on PQ-induced acute lung injury through inhibiting inflammation, oxidative stress and fibrosis by regulating NF-κB pathway.

Carbon monoxide-releasing molecule-2 suppresses thrombomodulin and endothelial protein C receptor expression of human umbilical vein endothelial cells induced by lipopolysaccharide in vitro.

OBJECTIVE: The aim of this study was to observe the counter-effect of carbon monoxide-releasing molecule-2 (CORM-2) on lipopolysaccharide (LPS)-suppressed thrombomodulin (TM) and endothelial protein C receptor (EPCR) expressions from human umbilical vein endothelial cell (HUVEC), and to reveal its mechanisms. METHODS: HUVECs were divided into 5 treatment groups, wherein reagents were added simultaneously. TM and EPCR proteins of the cells and the culture medium levels of soluble TM, soluble EPCR, and matrix metalloproteinase-2 (MMP-2) were detected after administration, whereas mRNA levels of TM and EPCR, as well as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activity among groups, were also evaluated. RESULTS: No significant difference was observed in any indicator between CORM-2 and sham groups. Addition of LPS produced drastic increase in MMP-2 expression, NF-κB activity, shedding of TM and EPCR (into the culture medium), as well as remarkable decrease in both mRNA and protein expressions of TM and EPCR, and cell viability. LPS + CORM-2 treatment significantly reduced the increase in MMP-2, NF-κB activity, and TM/EPCR shedding, whereas maintained both mRNA and protein levels of TM and EPCR, and preserved cell viability. CONCLUSIONS: CORM-2 protects HUVEC from LPS-induced injury, by way of suppressing NF-κB activity, which downregulates TM and EPCR mRNAs. It also decreases MMP-2 expression and prevents the shedding of TM and EPCR from the surface of endothelial cells, so as to preserve their protective effect.

Resveratrol ameliorates LPS-induced acute lung injury via NLRP3 inflammasome modulation.

NLRP3 inflammasome plays a pivotal role in the development of acute lung injury (ALI), accelerating IL-1ß and IL-18 release and inducing lung inflammation. Resveratrol, a natural phytoalexin, has anti-inflammatory properties via inhibition of oxidation, leukocyte priming, and production of inflammatory mediators. In this study, we aimed to investigate the effect of resveratrol on NLRP3 inflammasome in lipopolysaccharide-induced ALI. Mice were intratracheally instilled with 3mg/kg lipopolysaccharide (LPS) to induce ALI. Resveratrol treatment alleviated the LPS-induced lung pathological damage, lung edema and neutrophil infiltration. In addition, resveratrol reversed the LPS-mediated elevation of IL-1ß and IL-18 level in the BAL fluids. In lung tissue, resveratrol also inhibited the LPS-induced NLRP3, ASC, caspase-1 mRNA and protein expression, and NLRP3 inflammasome activation. Moreover, resveratrol administration not only suppressed the NF-κB p65 nuclear translocation, NF-κB activity and ROS production in the LPS-treated mice, but also inhibited the LPS-induced thioredoxin-interacting protein (TXNIP) protein expression and interaction of TXNIP-NLRP3 in lung tissue. Meanwhile, resveratrol obviously induced SIRT1 mRNA and protein expression in the LPS-challenged mice. Taken together, our study suggests that resveratrol protects against LPS-induced lung injury by NLRP3 inflammasome inhibition. These findings further suggest that resveratrol may be of great value in the treatment of ALI and a potential and an effective pharmacological agent for inflammasome-relevant diseases.