Safeguarding intestine cells against enteropathogenic Escherichia coli by intracellular protein reaction, a preventive antibacterial mechanism.

A critical problem in the fight against bacterial infection is the rising rates of resistance and the lack of new antibiotics. The discovery of new targets or new antibacterial mechanisms is a potential solution but is becoming more difficult. Here we report an antibacterial mechanism that safeguards intestine cells from enteropathogenic Escherichia coli (EPEC) by shutting down an infection-responsive signal of the host intestine cell. A key step in EPEC infection of intestinal cells involves Tir-induced actin reorganization. Nck mediates this event by binding with Tir through its SH2 domain (Nck-SH2) and with WIP through its second SH3 domain (Nck-SH3.2). Here we report the design of a synthetic peptide that reacts precisely with a unique cysteine of the Nck-SH3.2 domain, blocks the binding site of the Nck protein, and prevents EPEC infection of Caco-2 cells. Oral update of this nontoxic peptide before EPEC administration safeguards mice from EPEC infection and diarrhea. This study demonstrates domain-specific blockage of an SH3 domain of a multidomain adaptor protein inside cells and the inhibition of Tir-induced rearrangement of the host actin cytoskeleton as a previously unknown antibacterial mechanism.

ALK is required for NLRP3 inflammasome activation in macrophages.

The NLRP3 inflammasome is a key mediator of host immune responses through the induction of pyroptosis and the release of cytokines. Although the pathologic role of inflammasome in infection and sterile inflammation is well known, the mechanism and regulation of NLRP3 inflammasome activation remains obscure. Here, we report that anaplastic lymphoma kinase (ALK) is a novel regulator of NLRP3 inflammasome activation in macrophages. Pharmacologic or genetic inhibition of ALK through targeted drugs (ceritinib and lorlatinib) or RNAi blocked extracellular ATP-induced NLRP3 inflammasome activation in macrophages. Mechanically, ALK-mediated NF-κB activation was required for the priming step of NLRP3 upregulation, whereas ALK-mediated lipid peroxidation contributed to the sensing step of NLRP3-NEK7 complex formation. These studies indicate that inhibition of ALK could be utilized to treat NLRP3-related inflammatory diseases.

The combination of osthole with baicalin protects mice from Staphylococcus aureus pneumonia.

We reported the inhibition of α-Hemolysin (Hla) production in methicillin-resistant Staphylococcus aureus USA300 by osthole and further investigated the combination of osthole and baicalin in the treatment of staphylococcal pneumonia. Using cytotoxicity assays and a mouse model of intranasal lung infection, we evaluated the effect of combined therapy. Our results suggest that the combination of osthole and baicalin alleviated S. aureus-mediated A549 cell injury and protected mice from S. aureus pneumonia.

Betulin protects mice from bacterial pneumonia and acute lung injury.

Betulin, a naturally occurring triterpene, has shown anti-HIV activity, but details on the anti-inflammatory activity are scanty. In this study, we sought to investigate the effect of Betulin on LPS-induced activation of cell lines with relevance for lung inflammation in vitro and on lung inflammation elicited by either LPS or viable Escherichia coli (E. coli) in vivo. In vitro, Betulin inhibited LPS-induced tumor necrosis factor α (TNF-α) and (interleukin) IL-6 levels and up-regulated the level of IL-10. Also Betulin suppressed the phosphorylation of nuclear factor-κB (NF-κB) p65 protein in LPS-stimulated RAW 264.7 cells. In vivo, Betulin alleviated LPS-induced acute lung injury. Treatment with Betulin diminished pro-inflammatory cytokines, myeloperoxidase activity and bacterial loads in lung tissue during gram-negative pneumonia. Our findings demonstrated that Betulin inhibits pro-inflammatory responses induced by the gram-negative stimuli LPS and E. coli, suggesting that Betulin may represent a novel strategy for the treatment of lung inflammation.

JOINEDTrans: Prior guided multi-task transformer for joint optic disc/cup segmentation and fovea detection.

Deep learning-based image segmentation and detection models have largely improved the efficiency of analyzing retinal landmarks such as optic disc (OD), optic cup (OC), and fovea. However, factors including ophthalmic disease-related lesions and low image quality issues may severely complicate automatic OD/OC segmentation and fovea detection. Most existing works treat the identification of each landmark as a single task, and take into account no prior information. To address these issues, we propose a prior guided multi-task transformer framework for joint OD/OC segmentation and fovea detection, named JOINEDTrans. JOINEDTrans effectively combines various spatial features of the fundus images, relieving the structural distortions induced by lesions and other imaging issues. It contains a segmentation branch and a detection branch. To be noted, we employ an encoder with prior-learning in a vessel segmentation task to effectively exploit the positional relationship among vessel, OD/OC, and fovea, successfully incorporating spatial prior into the proposed JOINEDTrans framework. There are a coarse stage and a fine stage in JOINEDTrans. In the coarse stage, OD/OC coarse segmentation and fovea heatmap localization are obtained through a joint segmentation and detection module. In the fine stage, we crop regions of interest for subsequent refinement and use predictions obtained in the coarse stage to provide additional information for better performance and faster convergence. Experimental results demonstrate that JOINEDTrans outperforms existing state-of-the-art methods on the publicly available GAMMA, REFUGE, and PALM fundus image datasets. We make our code available at https://github.com/HuaqingHe/JOINEDTrans.

Site-Selective Tyrosine Reaction for Antibody-Cell Conjugation and Targeted Immunotherapy.

Targeted immunotherapies capitalize on the exceptional binding capabilities of antibodies to stimulate a host response that effectuates long-lived tumor destruction. One example is the conjugation of immunoglobulins (IgGs) to immune effector cells, which equips the cells with the ability to recognize and accurately kill malignant cells through a process called antibody-dependent cellular cytotoxicity (ADCC). In this study, a chemoenzymatic reaction is developed that specifically functionalizes a single tyrosine (Tyr, Y) residue, Y296, in the Fc domain of therapeutic IgGs. A one-pot reaction that combines the tyrosinase-catalyzed oxidation of tyrosine to o-quinone with a subsequent [3+2] photoaddition with vinyl ether is employed. This reaction installs fluorescent molecules or bioorthogonal groups at Y296 of IgGs or the C-terminal Y-tag of an engineered nanobody. The Tyr-specific reaction is utilized in constructing monofunctionalized antibody-drug conjugates (ADCs) and antibody/nanobody-conjugated effector cells, such as natural killer cells or macrophages. These results demonstrate the potential of site-selective antibody reactions for enhancing targeted cancer immunotherapy.

Modulating Liquid-Liquid Phase Separation of Nck Adaptor Protein against Enteropathogenic Escherichia coli Infection.

Signaling proteins often form biomolecular condensates through liquid-liquid phase separation (LLPS) during intracellular signal transduction. Modulating the LLPS property of intracellular protein condensates will redirect intracellular signals and provide a potential way to regulate cellular physiology. Phosphorylation of multiple tyrosine residues of the transmembrane receptor nephrin is known to drive the LLPS of the adaptor protein Nck and neuronal Wiskott-Aldrich Syndrome protein (N-WASP) and form the Nck signaling complex. Phosphorylation of the translocated intimin receptor (Tir) in the host cell may recruit this enteropathogenic Escherichia coli (EPEC) virulence factor to the Nck signaling complex and lead to the entry of EPEC into the intestine cell. In this work, we first identified a phosphotyrosine (pY)-containing peptide 3pY based on the sequence similarity of nephrin and Tir; 3pY promoted the LLPS of Nck and N-WASP, mimicking the role of phosphorylated nephrin. Next, we designed a covalent blocker of Nck, peptide p1 based on the selected pY peptides, which site-selectively reacted with the SH2 domain of Nck (Nck-SH2) at Lys331 through a proximity-induced reaction. The covalent reaction of p1 with Nck blocked the protein binding site of Nck-SH2 and disintegrated the 3pY/Nck/N-WASP condensates. In the presence of membrane-translocating peptide L17E, p1 entered Caco-2 cells in the cytosol, reduced the number of Nck puncta, and rendered Caco-2 cells resistant to EPEC infection. Site-selective covalent blockage of Nck thereby disintegrates intracellular Nck condensates, inhibits actin reorganization, and shuts down the entrance pathway of EPEC. This work showcases the promotion or inhibition of protein phase separation by synthetic peptides and the use of reactive peptides as LLPS disruptors and signal modulators.

Platelet-activating factor antagonist-based intensive antiplatelet strategy in acute ischemic stroke: A propensity score matched with network pharmacology analysis.

BACKGROUND: Diterpene ginkgolides meglumine injection (DGMI) is a platelet-activating factor receptor (PAFR) antagonist that can be used to treat acute ischemic stroke (AIS). This study evaluated the efficacy and safety of an intensive antiplatelet strategy based on PAFR antagonists and explored the underlying mechanisms of PAFR antagonists in AIS treatment. METHODS: This is a retrospective study applying propensity score methods to match AIS patients treated with DGMI to nontreated patients. The primary outcome was functional independence (modified Rankin Scale [mRS] 0-2) at 90 days. The safety outcome was bleeding risk. We used McNemar test to compare the efficacy outcome. Subsequently, the network pharmacology analysis was performed. RESULTS: 161 AIS patients treated with DGMI in the study were matched with 161 untreated patients. Compared with untreated patients, DGMI-treated patients had a significantly higher rate of mRS ranking 0-2 at 90 days (82.0% vs. 75.8%, p < 0.001), without increased risk of bleeding. The gene enrichment analysis showed that the overlap genes of DGMI targeted and AIS-related enriched in thrombosis and inflammatory-related signaling pathways. CONCLUSIONS: An intensive antiplatelet strategy of DGMI plus traditional antiplatelet agents is effective in treating AIS and may work by mediating post-stroke inflammation and thrombosis.

Covalent Reactive Peptides to Block Protein-Protein Interactions and Inhibit Microbe-Host Interaction.

A key step in enteropathogenic Escherichia coli (EPEC) infection of intestinal cells involves a Tir-induced actin reorganization. Nck mediates this event by binding with WIP through its second SH3 domain (Nck-SH3.2). Recently we have developed a preventative antibacterial mechanism that safeguards intestinal cells by shutting down this intracellular signal through a site-selective covalent peptide-protein reaction, a new antibacterial strategy that acts on the host cells instead of bacterium cells. Here we present the experimental details of the design and synthesis of cysteine-reactive peptides to selectively block Nck-SH3.2 but not the other two SH3 domains. Procedures of EPEC infection, covalent reaction inside Caco-2 cells, and bacterial counting to check the antibacterial effect are also described.

Possible indicators of amputation and insufficient perfusion after heat press injury: A retrospective study.

INTRODUCTION: Amputation outcome after heat press injury is associated with insufficient perfusion. We aimed to determine other risk factors for heat press injury and mechanisms of insufficient perfusion associated with amputation. METHODS: We retrospectively classified 120 inpatients into the emergency and clinic groups, with arrival time before and after 48 h of injury, respectively. We performed propensity score-match to identify significant variables and combine them with those previously identified. Patients with or without amputation were categorized in different subgroups according to arrival time and perfusion with receiver-operator-characteristic (ROC) curves. RESULTS: In the emergently insufficient perfusion subgroup, red blood cell distribution width of standard deviation (RDW-SD) was statistically different between patients without and with amputation (cutoff = 43 fL; specificity = 0.909). In the urgent group, neutrophil-lymphocyte-ratio (NLR) and relative lymphocyte count (L%) showed no association with perfusion, but was associated with amputation (NLR cutoff value = 3.12; sensitivity = 0.846). Differential leukocytes and related ratios (both groups), D-dimer (emergency group), and creatine kinase (CK) (clinic group) were also associated with insufficient perfusion. CONCLUSION: The study showed some correlations. Inflammation variables, D-dimer, and CK were associated with amputation and perfusion after heat press injury. Several factors were associated with amputation, including RDW-SD increase in insufficiently perfused patients within 48 h of injury, and NLR increase and L% decrease in patients after 48 h post-injury.

Different Depths May Not Determine the Fluid Resuscitation Volume in Early-stage Management of Severe Burns: A Model-comparison Retrospective Analysis of Fluid Volume Determining Factors.

Large-volume fluid resuscitation remains irreplaceable in the early-stage management of severe burns. We aimed to explore the relationship between fluid volume and other indicators. Data of severe burn patients with successful resuscitation in the early stage was collected. Correlation and linear regression analyses were performed. Multiple linear regression models, related goodness-of-fit assessment (adjusted R-square and Akaike Information Criterion), scatter plots, and paired t-test for two models, and a likelihood ratio test were performed. 96 patients were included. The median of total burn area (TBA) was 70%TBSA, with full thickness burn area (FTBA)/TBA of 0.4, a resuscitation volume of 1.93 mL/kg/%TBSA. Among volume-correlated indicators, two linear regression models were established (Model 1: TBA × weight and tracheotomy; and Model 2: FTBA × weight, partial thickness burn area (PTBA) × weight, and tracheotomy). For these models, close values of Akaike Information Criterion, adjusted R-squares, outliers of the prediction range, and the result of paired t-test, all suggest similarity between two models estimations, while the likelihood ratio test for coefficients of FTBA × weight and PTBA × weight showed a statistical difference. Inhalational injury and decompression surgery only correlated with volume, while Tracheotomy, TBA × weight, FTBA × weight, and PTBA × weight correlated with and were accepted in linear models of volume. Although FTBA and PTBA differed statistically, there may be no need to distinguish them when estimating the resuscitation volume requirements in this patient set. Further study about different depths fluid should be conducted.

Expression profile, clinical significance and biological functions of IGF2BP2 in esophageal squamous cell carcinoma.

The ectopic expression of insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) has been demonstrated to facilitate tumorigenesis and induce proliferation in a various types of cancer. However, the role of IGF2BP2 in esophageal squamous cell carcinoma (ESCC) has yet been fully elucidated. In this regard, the current study assessed the expression patterns and clinical significance of IGF2BP2 in 94 Chinese patients diagnosed with ESCC. Immunohistochemistry and reverse transcription-quantitative PCR assays were employed to assess IGF2BP2 expression in ESCC tissues compared with adjacent healthy tissues. The results revealed that the protein expression of IGF2BP2 was substantially upregulated in ESCC tissues compared with adjacent ESCC tissues. More specifically, higher IGF2BP2 expression strongly associated with tumor node metastasis stage, lymphatic infiltration and lymph node metastasis. Using two ESCC cell lines (TE-1 and TE-10), the inhibition of IGF2BP2 expression by small interfering RNA was proven to induce apoptosis and suppress proliferation, migration and cell cycle progression in vitro. Collectively, the present findings indicated that IGF2BP2 may serve a major role in the development of ESCC carcinogenesis. The present study may be helpful in the design of potential drug targets in the treatment of ESCC.

Conventional, diffusion, and dynamic contrast-enhanced MRI findings for differentiating metaplastic Warthin's tumor of the parotid gland.

The purpose of this study was to explore conventional, diffusion, and dynamic contrast-enhanced MRI (DCE-MRI) characteristics for differentiating metaplastic Warthin's tumor (MWT) from other tumor types of the parotid gland, including non-metaplastic Warthin's tumor (non-MWT), pleomorphic adenoma (PA), and malignant tumor (MT). A total of 178 patients with histologically proven tumors of the parotid gland, including 21 MWTs, 49 non-MWTs, 66 PAs, and 42 MTs, were enrolled in the study. Conventional MRI was performed in all patients. One hundred and fifty patients had preoperative diffusion-weighted MR imaging (DWI), and 62 patients had preoperative DCE-MRI. The differences in the conventional, DCE-MRI, and DWI records between MWTs and the other three tumor types were statistically evaluated. Compared with non-MWTs and PAs, there was a statistically significant difference in circumscription (p < 0.01). The ill-defined circumscription was more common in MWTs than non-MWTs and PAs. Compared with PAs, there was a statistically significant difference in morphology (p < 0.05). The lobulated morphology was more common in PAs than MWTs. Compared with PAs and MTs, there was a statistically significant difference in the T2 signal of the solid component (p < 0.01). The T2 moderate intensity of solid components was more common in MWTs than PAs and MTs. The solid components of PAs mostly showed hyperintense on T2-weighted imaging. Cyst/necrosis was more common in MWTs than PAs and MTs. Hyperintense of cyst/necrosis was more common in MWTs and non-MWTs. With respect to contrast enhancement, 52.4% MWTs exhibited moderate or marked enhancement, and most non-MWTs (81.6%) exhibited mild enhancement. Most PAs (84.8%) exhibited marked enhancement. The mean ADC value of MWTs (0.94 × 10-3 ± 0.11 mm2/s) was significantly lower than that of the PAs (1.60 × 10-3 ± 0.17 mm2/s) (p < 0.001). On DCE-MRI, six of eight MWTs demonstrated TIC of type B. Although MWT is rare, conventional MRI characteristics, DWI and DCE-MRI can provide useful information for differentiating MWT from other parotid mass.

Circulating HPV cDNA in the blood as a reliable biomarker for cervical cancer: A meta-analysis.

The applications of liquid biopsy have attracted much attention in biomedical research in recent years. Circulating cell-free DNA (cfDNA) in the serum may serve as a unique tumor marker in various types of cancer. Circulating tumor DNA (ctDNA) is a type of serum cfDNA found in patients with cancer and contains abundant information regarding tumor characteristics, highlighting its potential diagnostic value in the clinical setting. However, the diagnostic value of cfDNA as a biomarker, especially circulating HPV DNA (HPV cDNA) in cervical cancer remains unclear. Here, we performed a meta-analysis to evaluate the applications of HPV cDNA as a biomarker in cervical cancer. A systematic literature search was performed using PubMed, Embase, and WANFANG MED ONLINE databases up to March 18, 2019. All literature was analyzed using Meta Disc 1.4 and STATA 14.0 software. Diagnostic measures of accuracy of HPV cDNA in cervical cancer were pooled and investigated. Fifteen studies comprising 684 patients with cervical cancer met our inclusion criteria and were subjected to analysis. The pooled sensitivity and specificity were 0.27 (95% confidence interval [CI], 0.24-0.30) and 0.94(95% CI, 0.92-0.96), respectively. The pooled positive likelihood ratio and negative likelihood ratio were 6.85 (95% CI, 3.09-15.21) and 0.60 (95% CI, 0.46-0.78), respectively. The diagnostic odds ratio was 15.25 (95% CI, 5.42-42.94), and the area under the summary receiver operating characteristic curve was 0.94 (95% CI, 0.89-0.99). There was no significant publication bias observed. In the included studies, HPV cDNA showed clear diagnostic value for diagnosing and monitoring cervical cancer. Our meta-analysis suggested that detection of HPV cDNA in patients with cervical cancer could be used as a noninvasive early dynamic biomarker of tumors, with high specificity and moderate sensitivity. Further large-scale prospective studies are required to validate the factors that may influence the accuracy of cervical cancer diagnosis and monitoring.

Self-supervised iterative refinement learning for macular OCT volumetric data classification.

We present self-supervised iterative refinement learning (SIRL) as a pipeline to improve a type of macular optical coherence tomography (OCT) volumetric image classification algorithms. In this type of algorithms, first, two-dimensional (2D) image classification algorithms are applied to each B-scan in an OCT volume, and then B-scan level classification results are combined to obtain the classification result of the volume. Specifically, SIRL consists of repetitive training-sieving-relabeling steps. In the initialization stage, the label of each 2D image is assigned as the label of the volume they belong to, yielding an initial label set. In the training stage, the network is trained using the current label set. In the sieving and relabeling stage, the label of each 2D image is renewed based on the classification result of the trained network, and a new label set is obtained. Experiments are conducted on a clinical dataset and public dataset, on which the performances of the models trained by a normal scheme and our proposed methods are compared under a five-fold cross validation. Our proposed method achieves sensitivity, specificity, and accuracy of 89.74%, 94.87%, and 93.18%, respectively, on the clinical dataset. On the public dataset, the results of the corresponding three metrics are 98.22%, 90.43% and 95.88%. The results demonstrate the effectiveness of our proposed method as an approach to improve the B-scan-classification-based macular OCT volumetric image classification algorithms.

Intensification of hydrological drought due to human activity in the middle reaches of the Yangtze River, China.

Hydrological extremes are changing under the impacts of environmental change, i.e., climate variation and human activity, which can substantially influence ecosystems and the living environment of humans in affected region. This study investigates the impacts of environmental change on hydrological drought in the middle reaches of the Yangtze River in China based on hydrological modelling. Change points for streamflow into two major lakes and a reservoir in the study area were detected in the late 1980s using the Mann-Kendall test. Streamflow simulation by a water balance model was performed, and the resulting Kling-Gupta efficiency value was >0.90. Hydrological drought events were identified based on the simulated streamflow under different scenarios. The results show that the hydrological drought occurrence was increased by precipitation, whereas the drought peak value was increased by potential evapotranspiration. The impacts of precipitation and potential evapotranspiration on drought severity and duration varied in the study area. However, hydrological drought was intensified by the influence of human activity, which increased the severity, duration and peak value of droughts. The dominant factor for hydrological drought severity is precipitation, followed by potential evapotranspiration and human activity. The impacts of climate variation and human activity on drought severity are larger than on drought duration. In addition, environmental change is shown to have an "accumulation effect" on hydrological drought, demonstrating that the indirect impacts of environmental change on hydrological drought are much larger than the direct impacts on streamflow. This study improves our understanding of the responses of hydrological extremes to environmental change, which is useful for the management of water resources and the prediction of hydrological disasters.

MiR-26b regulates 5-FU-resistance in human colorectal cancer via down-regulation of Pgp.

Chemotherapy resistance frequently drives tumor progression. However, the underlying molecular mechanisms remain unclear. In this study, we found that the expression level of miR-26b was down-regulated in the human colorectal cancer tissues and the resistant cells strains: HT-29/5-FU and LOVO/5-FU cells. Meanwhile, we showed that miR-26b improved sensibility of colorectal cancer cells to 5-FU in vitro and enhanced the potency of 5-FU in the inhibition of tumor growth in vivo. We further demonstrated that the tumor suppressive role of miR-26b was mediated by negatively regulating P-glycoprotein (Pgp) protein expression. Furthermore, studies of colorectal cancer specimens indicated that the expression of miR-26b and Pgp had inverse correlation. Importantly, we found that CpG islands in the miR-26b promoter region were hypermethylated in 5-FU resistant cells. Our study is the first to identify the tumor suppressive role of over-expressed miR-26b in chemo-sensitivity. Identification of a novel miRNA-mediated pathway that regulates chemo-sensitivity in colorectal cancer will facilitate the development of novel therapeutic strategies in the future.

Pretreatment with the compound asperuloside decreases acute lung injury via inhibiting MAPK and NF-κB signaling in a murine model.

Asperuloside, an iridoid glycoside found in Herba Paederiae, is a component from traditional Chinese herbal medicine. In this study, we aimed to investigate the protective effects and potential mechanisms of asperuloside action on inflammatory responses in lipopolysaccharide (LPS)-stimulated Raw 264.7 cells and an LPS-induced lung injury model. The pro-inflammatory cytokines and signaling pathways were measured by enzyme-linked immunosorbent assays (ELISA) and Western blotting to determine the effects of asperuloside. We found that asperuloside can significantly downregulate tumor necrosis factor alpha (TNF-α), interleukin (IL)-1ß, and IL-6 levels in vitro and in vivo, and treatment with asperuloside significantly reduced the lung wet-to-dry weight, histological alterations and myeloperoxidase activity in a murine model of LPS-induced acute lung injury (ALI). In addition, Western blot analysis that pretreatment with asperuloside remarkably blunted the phosphorylation of inhibitor of nuclear factor kappa-B (IκBα), extracellular signal-related kinases 1 and 2 (ERK1/2), c-Jun. N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38MAPK) in LPS-stimulated inflammation. These results indicate that asperuloside exerts its anti-inflammatory effect in correlation with inhibition of a pro-inflammatory mediator through suppressing nuclear factor kappa-B (NF-κB) nuclear translocation and MAPK phosphorylation in a dose-dependent manner.

Therapeutic effects of rosmarinic acid on airway responses in a murine model of asthma.

Rosmarinic acid (RA) is an active component of a traditional Chinese herbal medicine. Previously, we reported that RA exerted a strong anti-inflammatory effect in a mouse acute lung injury model. Therefore, we hypothesized that RA might also have potential therapeutic effects in a murine model of asthma. In this study, we aimed to evaluate the anti-asthmatic activity of RA and explored its possible molecular mechanisms of action. Female BALB/c mice that had been sensitized to and challenged with ovalbumin (Ova) were treated with RA (20mg/kg) 1h after challenge. The results showed that RA greatly diminished the number of inflammatory cells and the production of Th2 cytokines in the bronchoalveolar lavage fluid (BALF); significantly reduced the secretion of total IgE, Ova-specific IgE, and eotaxin; and markedly ameliorated airway hyperresponsiveness (AHR) compared with Ova-induced mice. Histological studies further revealed that RA substantially decreased inflammatory cells infiltration and mucus hypersecretion compared with Ova-induced mice. Moreover, our results suggested that the protective effects of RA were mediated by the inhibition of JNK and p38 MAPK phosphorylation and nuclear factor-κB (NF-κB) activation. Furthermore, RA treatment resulted in a significant reduction in the mRNA expression of AMCase, CCL11, CCR3, Ym2 and E-selectin in lung tissue. These findings suggest that RA may effectively delay the development of airway inflammation and could thus be used as a therapy for allergic asthma.

D(-)-Salicin inhibits the LPS-induced inflammation in RAW264.7 cells and mouse models.

D(-)-Salicin is a traditional medicine which has been known to exhibit anti-inflammation and other therapeutic activities. The present study aimed to investigate whether D(-)-Salicin inhibited the LPS-induced inflammation in vivo and in vitro. We evaluated the effect of D(-)-Salicin on cytokines (TNF-α, IL-1ß, IL-6 and IL-10) in vivo and in vitro by enzyme-linked immunosorbent assay and signaling pathways (MAPKs and NF-κB) in vivo by Western blot. The results showed that D(-)-Salicin markedly decreased TNF-α, IL-1ß and IL-6 concentrations and increased IL-10 concentration. In addition, western blot analysis indicated that D(-)-Salicin suppressed the activation of MAPKs and NF-κB signaling pathways stimulated by LPS. To examine whether D(-)-Salicin ameliorated LPS-induced lung inflammation, inhibitors of MAPKs and NF-κB signaling pathways were administrated intraperitoneally to mice. Interference with specific inhibitors revealed that D(-)-Salicin-mediated cytokine suppression was through MAPKs and NF-κB pathways. In the mouse model of acute lung injury, histopathologic examination indicted that D(-)-Salicin suppressed edema induced by LPS. So it is suggest that D(-)-Salicin might be a potential therapeutic agent against inflammatory diseases.