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B7-H3 has emerged as a promising target for cancer immunotherapy. We assessed the role of B7-H3 expression in tumour-infiltrating immune cells in non–small-cell lung cancer (NSCLC). Tumour-infiltrating immune cell characterisation was performed by flow cytometry in a prospective cohort, whereas the relationship between B7-H3 expression and clinicopathological features was explored in a retrospective cohort. B7-H3 expression was detected in tumour/epithelial cells and immune cells, including macrophages, monocytes, dendritic cells (DCs) and myeloid-derived suppressor cells. B7-H3 was expressed at higher levels in cells within the tumour than in cells within non-neoplastic tissues. B7-H3 expression score in tumour cells positively correlated with the amount of CD45+ immune cells (rho = 0.305, P = 0.010), CD8+ T-cells (rho = 0.330, P = 0.005), and the percentage of CD8+/CD3+ T-cells (rho = 0.403, P < 0.001). Patients with high tumoural B7-H3 expression showed increased numbers of immune cells (P = 0.002), CD8+ T-cells (P = 0.011), natural killer cells (P = 0.073) and plasmacytoid DCs (P = 0.015). Tumoural B7-H3 expression was higher in males, smokers, squamous cell carcinomas, tumours with wild-type EGFR , poor differentiation, larger size and nodal metastasis (P < 0.05, all). Tumoural B7-H3 expression was associated with PD-L1 expression (P = 0.001), shorter 5-year overall survival (P = 0.012) and poor survival after anti–PD-1 blockade (P = 0.026). Tumoural B7-H3 overexpression was associated with increased tumour-infiltrating cytotoxic lymphocytes and poor prognosis in NSCLC. Thus, B7-H3 is a promising prognostic biomarker and immunotherapeutic target in NSCLC. • B7-H3–related tumour immune microenvironment was comprehensively analysed in non–small-cell lung cancer (NSCLC). • B7-H3 expression is higher in cells within tumour than those within non-neoplastic tissue. • NSCLC with B7-H3 overexpression was highly infiltrated by cytotoxic lymphoid cells and antigen presenting cells. • B7-H3 overexpression was associated with adverse clinicopathological feature in NSCLC. • B7-H3 overexpression was associated with poor prognosis in patients with resected NSCLC or in those received PD-1 blockade. [ABSTRACT FROM AUTHOR]

Raman spectroscopy is non-destructive method that allows monitoring of biological tissues with minimal intervention. FT-Raman (λ ex 1064 nm) and NIR-Vis-Raman (λ ex 785 nm) spectroscopic measurements were used in ex vivo analysis of normal, non-cancerous abnormal and cancerous lung tissues. Spectroscopic discrimination of the lung tissue samples was made by the use of the ratio of characteristic bands and multivariate statistical methods (PCA, LDA). The combination of Raman spectroscopy and multivariate statistics may have a diagnostic potential for recognizing of cancer lesions in lung. Unlabelled Image • Raman spectroscopy allows monitoring of biological tissues with minimal intervention. • Raman measurements at λ ex 1064 nm and 785 nm were used in ex vivo analysis of lung tissues. • Normal, non-cancerous abnormal and cancerous samples were discriminated by statistical evaluation of the spectra. • Raman spectroscopy may have a diagnostic potential for recognizing of cancer lesions in lung. [ABSTRACT FROM AUTHOR]

Acute lung injury (ALI), a persistent lung inflammatory response syndrome, may evolve into acute respiratory distress syndrome (ARDS). Characterized by rapid onset, critical features, and a complex etiology, ALI remains a challenging critical respiratory disease. Recently, mesenchymal stem cells (MSCs) have provided a new solution for the treatment of ALI. We built a lipopolysaccharide (LPS)-induced ALI model in mice. After treatment with human umbilical cord mesenchymal stem cells (hUC-MSCs), FTY720, or a combination of hUC-MSCs and FTY207, the lung inflammatory response was apparently attenuated. To understand the mechanism underlying MSCs treatment of ALI at the genetic level, significant differentially expressed long non-coding RNAs (lncRNAs) between the treatment and model groups were analyzed using microarray technology. Moreover, genetic gene prediction, gene ontology (GO) analysis, pathway analysis, and transcription factor (TF) prediction were carried out. The results showed that a total of 66 lncRNAs were differentially expressed in all three treatment groups, including 8 up-regulated and 58 down-regulated lncRNAs. LncRNA A_30_P01029806 and A_30_P01029194, which were down-regulated, were involved in the signaling pathways closely related to ALI. Through further TF analysis, we identified several significant TFs which lay a foundation for revealing the mechanism underlying lncRNAs treatment of ALI. LncRNA A_30_P01029806 and A_30_P01029194 may serve as candidate biomarkers in the diagnosis and treatment of ALI. • 66 lncRNAs were differentially expressed in all three treatment groups. • Two lncRNAs were involved in the signaling pathways closely related to ALI. • Several significant TFs related to the two lncRNAs were identified through TF prediction. • The two lncRNAs may serve as candidate biomarkers in the diagnosis and treatment of ALI. [ABSTRACT FROM AUTHOR]

• dp -BREATH provides well-segmented lung regions by classifying superpixels in CT scans. • dp -BREATH models pathological lung patterns as a Gaussian Mixing Model. • dp -Breath gives the probability of a region to contain each pathology being analyzed. • dp -BREATH highlights abnormal superpixel regions within the CT scan using heat maps. • Highlighted regions provide probabilities information regarding abnormal findings. Background and Objective: Identifying abnormalities in chest CT scans is an important and challenging task, demanding time and effort from specialists. Different parts of a single lung image may present both normal and abnormal characteristics. Thus, detecting a single lung as healthy (normal) or not is inaccurate. Methods: In this work we propose dp- BREATH, a method capable of detecting abnormalities in pulmonary tissue regions and directing the specialist's attention to the lung region containing them. It starts by highlighting regions that may indicate pulmonary abnormalities based on the healthy pulmonary tissue behavior using a superpixel-based approach and a heat map visualization. This is achieved by modeling regions of healthy tissue using a statistical model. All regions considered abnormal are modeled and classified according to their probability of containing each of the studied abnormalities. Further, dp- BREATH provides a better recognition of radiological patterns, with the likelihood of a selected lung region to contain abnormalities. Results: We validate the statistical model of healthy and abnormal detection using a representative dataset of chest CT scans. The model has shown almost no overlap between healthy and abnormal regions, and the detection of abnormalities presented precision higher than 86%, for all recall values. Additionally, the fitted models describing pulmonary radiological patterns present precision of up to 87%, with a high separation for three of five radiological patterns. Conclusions: dp- BREATH's heat map representation and its list of radiological patterns probabilities provided are intuitive methods to assist physicians during diagnosis. [ABSTRACT FROM AUTHOR]

• CDC25C has prognostic value in lung adenocarcinoma based on data from the cancer genome atlas. • High CDC25C levels were associated with an advanced stage, lymph node invasion, distant metastasis, and poor status. • High CDC25C expression was associated with poor overall survival and progression-free survival. • CDC25C may be involved in LUAD via the regulation of the cell cycle and FAS -mediated apoptosis. Cell division cycle 25C (CDC25C) is involved in the regulation of the G2/M phase transition and is associated with various cancers, including non-small cell lung cancer. We evaluated its prognostic value in lung adenocarcinoma (LUAD) based on data from The Cancer Genome Atlas (TCGA). Kruskal–Wallis test, Wilcoxon signed-rank test, and logistic regression were used to evaluate relationships between clinical-pathologic features and CDC25C expression. Cox regression analyses and the Kaplan–Meier method were used to evaluate factors contributing to prognosis. Gene set enrichment analysis (GSEA) was performed. High CDC25C expression in LUAD was associated with a high tumor extent (odds ratio (OR) = 2.23 (1.52–3.29), P < 0.001), regional lymph node invasion (OR = 2.18 (1.48–3.22), P < 0.001), OR = advanced stage (OR = 2.47 (1.72–3.59), P < 0.001), and poor status (OR = 1.87 (1.19–2.96), P = 0.007). A univariate analysis showed that high CDC25C expression is associated with a short overall survival (OS) (HR: 1.873; 95% CI: 1.385–2.535; P < 0.001) and poor progression-free survival (HR: 1.503; 95% CI: 1.173–1.926; P = 0.0012). In a multivariate analysis, high CDC25C expression was associated with poor OS (HR = 2.193; CI: 1.394–3.452, P = 0.001). GSEA showed the enrichment of cell cycle, apoptosis, p53-dependent G1 DNA damage response, S-phase, mitotic M-M G1 phases, and FA-mediated cell death in the CDC25C high-expression phenotype. CDC25C predicts poor prognosis in LUAD and may function in cell cycle regulation and FAS-mediated apoptosis. [ABSTRACT FROM AUTHOR]

Highlights • Proposed approach is used to analyze shape changes of lung lesions over time. • Our methodology uses dynamic shape features to quantify changes of lung lesions. • Provide the specialist bigger support in studies on the biological activity of pulmonary nodules. Abstract Lung cancer remains one of the highest occurring cancers worldwide. Temporal assessment is a useful tool for analyzing the malignant behavior of a lesion during treatment, or for classifying previously unclassified lesions. This paper provides relatively detailed information about the changes in lesions, complementing the results of studies on the biological activity of pulmonary nodules. The methodology presented uses dynamic shape features (DSF) to quantify and analyze the changes in lung lesions over time as detected in computed tomography (CT) images. The study was conducted using two chest CT databases: the Public Lung Database (PLD), which contains images of lesions undergoing evaluation related to the patient's drug therapy, and a private database of images of lung lesions of undetermined diagnosis. The DSF parameters presented variance values in the range from 8.66 × 10 − 05 to 2.58 × 1006 in lesions in images in the private database, and in the range from 6.72 × 10 − 04 to 5.90 × 1010 in lesions images in the PLD. [ABSTRACT FROM AUTHOR]

Abstract Ethnopharmacological relevance In Asia, Jin Gui Shen Qi Wan (JGSQW) has been used for hundreds of years to treat asthma. Aim of the study The traditional Chinese medicine JGSQW is composed of Rehmannia glutinosa , Dioscorea opposita , Cornus officinalis , Poria cocos , Paeonia suffruticosa , Alisma orientalis , Aconitum carmichaelii and Cinnamomum cassia. However, the immunological mechanism underlying the effect of JGSQW treatment on asthma remains unclear. This study examined whether JGSQW has the potential to reduce asthma symptoms in mice with chronic asthma induced by recurrent Dermatophagoides pteronyssinus (Der p) stimulation, as well as its immunoregulatory mechanisms. Materials and methods The airways of BALB/c mice were stimulated with Der p (i.t.) once per week (50 μL, 1 mg/mL) for 6 consecutive weeks, and the mice were fed JGSQW (1 g/kg) 30 min prior to the Der p stimulation. Three days after the last stimulation, the mice were sacrificed to evaluate the airway remodelling, infiltration of inflammatory cells, lung histological features, and total IgE in the blood. Additionally, after A549 cells were treated with JGSQW, loganin, or paeoniflorin for 30 min, 10 ng/mL IL-1β was added to stimulate the A549 cells to evaluate the effect of the medicine on the ICAM-1 gene expression after IL-1β stimulation. Results JGSQW significantly reduced the Der p-induced infiltration of inflammatory cells into airways and decreased the total IgE and Der p-specific IgG1 in serum. Collagen assays and histopathological examinations showed that JGSQW reduced lung airway remodelling. Additionally, an electrophoretic mobility shift assay and immunohistochemical staining verified that JGSQW inhibited the NF-kB expression in airway epithelial cell nuclei. JGSQW, loganin, and paeoniflorin inhibited the ICAM-1 gene expression caused by the IL-1β stimulation of A549 cells, and loganin and paeoniflorin had the maximum inhibitory effect when mixed according to the combination of doses in JGSQW. Conclusion These results indicated that in the chronic asthma mouse model, JGSQW inhibits the infiltration of inflammatory cells into the airways and airway remodelling and exhibits specific immunoregulatory effects. JGSQW with certain doses of loganin and paeoniflorin inhibited ICAM-1 gene expression in epithelial cells. Graphical abstract fx1 [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Dilodendron bipinnatum Radlk., Sapindaceae, a tree of the Mato Grosso Pantanal , is popularly known as “mulher-pobre”. The decoction or infusion of its inner stem bark is used for treating inflammatory conditions. Aim of the study To determine if a 70% hydroethanolic extract of Dilodendron bipinnatum stem bark (HEDb) is able to reduce allergic airway inflammation in a murine model of ovalbumin (OVA)-induced allergic asthma. Material and methods The inner stem bark powder was macerated in a 70% hydroethanolic solution (1:3 w/v) to obtain HEDb. The induction of experimental asthma was accomplished as follows: on days 1 and 10, Swiss mice were sensitized by an intraperitoneal injection of OVA (100 µg/mL) and aluminum hydroxide (10 µg/mL). From day 19 to 24, animals (n = 6/per group) were treated (p.o.) twice a day with either vehicle (distilled water), HEDb (20, 100 and 500 mg/kg) or dexamethasone (0.5 mg/kg). Sham group animals were intraperitoneally injected and challenged with saline solution (0.9%) instead of OVA and received distilled water orally instead of HEDb, whereas the other groups were challenged with OVA (3% in saline) by aerosolization. On day 25, bronchoalveolar lavage fluid (BALF) was collected for the quantification of total leukocytes, neutrophils, eosinophils, mononuclear cells and Th2 cytokines (IL-4, IL-5, and IL-13). The lungs were collected for histopathological analysis and blood was assayed to determine serum IgE levels. The anti-inflammatory activity of HEDb was additionally confirmed by a lipoxygenase (LO) inhibitory assay in vitro. Results Compared to the sham group, the OVA group showed significantly greater numbers of total leukocytes, neutrophils, eosinophils, and mononuclear cells, as well as inflammatory cytokines in BALF, and also IgE in the serum. HEDb treated mice showed a significant decrease in inflammatory cell accumulation in BALF, with the maximum response observed at 500 mg/kg. Furthermore, the levels of IL-4, IL-5 and IL-13 in BALF, and of IgE in serum, were also considerably reduced as compared to the OVA group. The histopathological examination of the lungs of mice in the vehicle group showed a significant increase in hemorrhagic damage, mucus, perivascular and peribronchial inflammatory cell infiltrates, as well as mast cell degranulation compared to sham. HEDb (100 and 500 mg/kg) remarkably decreased all these parameters, presenting at the highest dose an anti-inflammatory effect comparable to that of dexamethasone (0.5 mg/kg). HEDb also had notable direct anti-inflammatory properties demonstrated by the inhibition of 15-LO activity in vitro (IC 50 = 1.0–5.0 µg/mL). Conclusions These results somewhat agree on the popular use of the inner stem bark of D. bipinnatum as a treatment for allergic asthma. The HEDb exhibits significant anti-inflammatory activity in the OVA-induced mouse model of allergic asthma, possibly due to the down-regulation of the Th2 responses and LO inhibition, resulting in improvements in all analyzed inflammatory parameters. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate quantitative computed tomography (CT) measurements of the lung parenchyma in lung transplant (LTx) patients for early detection of the bronchiolitis obliterans syndrome (BOS).Materials and Methods: 359 CT scans of 122 lung transplant patients were evaluated. Measurements of lung volume and density were performed for the whole lung and separately for each lobe. For longitudinal analysis the difference between the baseline at 6 months after LTx and follow-up examinations was calculated. Patients with and without BOS (matched 1:2) were compared at two different time points, the last examination before the BOS onset and the first examination within one year after BOS onset.Results: 30 patients developed BOS during the follow-up period. Longitudinal changes in the lung volume and lung density measured on CT differed significantly between those patients with and without early BOS, in particular the difference of the inspiratory and expiratory lung volume (p < 0.001), the ratio of the expiratory and inspiratory lung volume (p < 0.001-p = 0.001) and MLD (p < 0.001-p = 0.001), the volume on expiration (p < 0.001-p = 0.007), the MLD on expiration (p < 0.001-p = 0.007), and the percentiles on expiration (p < 0.001-p = 0.002) with an increase of lung volume and a decrease of lung density. Changes were pronounced in the lower lobes. Before BOS onset, patients with and without future development of BOS showed no significant differences.Conclusion: Longitudinal changes of lung volume and lung density measured on CT start markedly at BOS onset with increased lung volume and decreased lung density indicating increased inflation levels. Even though this method may help to diagnose BOS at onset it is not useful as a predictor for BOS before disease onset. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Cordyceps sinensis is a traditional Chinese medicine and has been used as adjuvant treatments for cancer and it has been also demonstrated to be effective in cancer patients. Aim of the study The objective of the present study is to investigate the anti-metastasis effects of water extracts of Cordyceps sinensis (WECS) in breast cancer and the potential mechanisms. Materials and methods The cytotoxicity of WECS on 4T1 breast cancer cells was evaluated in vitro using cell counting kit-8 (CCK8) assay. The in vivo anti-metastatic activity of intraperitoneally administered WECS and its effect on animal survival were measured in a mouse breast cancer metastasis model. To explore the molecular mechanisms of the anti-metastasis effect of WECS, the expression of matrix metalloprotein-9 (MMP-9) in serum was determined by enzyme-linked immunosorbent assay (ELISA). In addition, a protein array was used to examine the cytokine expression profiles in lung homogenates. Results Treatment with WECS (0.10–0.40 mg/ml) significantly inhibited 4T1 cell viability in vitro . In animal studies, 50 mg/kg WECS significantly reduced the number of metastatic lung nodules and the weight of lung, without affecting body weight of mice. Furthermore, WECS increased the survival rate of 4T1 tumor bearing mice in a dose dependent manner, and at high dose, WECS (50 mg/kg) significantly increased the life span of the mice compared to untreated control group. The expression level of MMP-9 in serum was decreased about 50% in 50 mg/kg WECS treated group compared to control group. The results of protein array showed that the expression of CC chemokine ligand 17 (CCL17), MMP-9, osteopontin (OPN), interleukin-33 (IL-33), CC chemokine ligand 12 (CCL12) and CC chemokine ligand 6 (CCL6) in the lungs of 4T1 tumor bearing mice was increased more than two fold compared with normal mice. Among them, the expression of CCL17, MMP-9, OPN, IL-33 was significantly reduced by treatment of 50 mg/kg WECS. Conclusion Our results demonstrated that WECS has potent anti-metastasis activity in a mouse breast cancer metastasis model possibly by down-regulation the expression of several metastasis-related cytokines. [ABSTRACT FROM AUTHOR]

Purpose: To compare analytic and Monte Carlo-based algorithms for proton dose calculations in the lung, benchmarked against anthropomorphic lung phantom measurements.Methods and Materials: A heterogeneous anthropomorphic moving lung phantom has been irradiated at numerous proton therapy centers. At 5 centers the treatment plan could be calculated with both an analytic and Monte Carlo algorithm. The doses calculated in the treatment plans were compared with the doses delivered to the phantoms, which were measured using thermoluminescent dosimeters and film. Point doses were compared, as were planar doses using a gamma analysis.Results: The analytic algorithms overestimated the dose to the center of the target by an average of 7.2%, whereas the Monte Carlo algorithms were within 1.6% of the physical measurements on average. In some regions of the target volume, the analytic algorithm calculations differed from the measurement by up to 31% in the internal gross target volume (iGTV) (46% in the planning target volume), over-predicting the dose. All comparisons showed a region of at least 15% dose discrepancy within the iGTV between the analytic calculation and the measured dose. The Monte Carlo algorithm recalculations showed dramatically improved agreement with the measured doses, showing mean agreement within 4% for all cases and a maximum difference of 12% within the iGTV.Conclusions: Analytic algorithms often do a poor job predicting proton dose in lung tumors, over-predicting the dose to the target by up to 46%, and should not be used unless extensive validation counters the consistent results of the present study. Monte Carlo algorithms showed dramatically improved agreement with physical measurements and should be implemented to better reflect actual delivered dose distributions. [ABSTRACT FROM AUTHOR]

Different acute respiratory distress syndrome (ARDS) phenotypes may explain controversial results in clinical trials. Lung-morphology is one of the ARDS-phenotypes and physiological studies suggest different responses in terms of positive-end-expiratory-pressure (PEEP) and recruitment-manoeuvres (RM) according to loss of aeration. To evaluate whether tailored ventilator regimens may impact ARDS outcomes, our group has designed a randomised-clinical-trial of ventilator settings according to lung morphology in moderate-to-severe ARDS (LIVE study). Method Patients will be enrolled within the first 12 hours of ARDS onset. In both groups, volume-controlled ventilation with low tidal-volumes (Vt) will be used to target a plateau pressure ≤ 30 cmH 2 O. In the control group, the PEEP level and inspired fraction of oxygen (FiO 2 ) will be set using the ARDSNet table; a Vt of 6 mL/kg of predicted body weight (PBW) will be set and prone position (PP) will be applied. In the intervention arm, the ventilator will be set according to lung morphology (focal/non-focal) that will be assessed according to CT-scan ± chest x-ray + lung echography. For focal ARDS patients, a Vt of 8 mL/kg PBW will be used along with low PEEP and PP. For non-focal ARDS patients, a Vt of 6 mL/kg PBW will be used with RM and PEEP to reach a plateau pressure ≤ 30 cmH 2 O. The primary outcome is all-cause 90-day mortality and the secondary outcomes are: in-hospital mortality, mortality at day 28, 60, 180 and 365; ventilator-free days at day 30, quality of life at one year; ventilator-associated pneumonia rate; barotrauma; ICU and hospital length of stay. This RCT is registered on Clinicaltrials.gov under identifier NCT02149589 . [ABSTRACT FROM AUTHOR]

Purpose To assess early time-related image findings in postmortem magnetic resonance imaging (MRI) and to evaluate observer agreement in a porcine model. Material and Methods Three pigs were examined by MRI at 15 different time points in the first 36 h after death. Two observers independently recorded the postmortem interval (PMI) to the appearance of fluid collection (pleural space, interlobar and interlobular pulmonary fissures and hepatic interlobar fissures), gas accumulation (intrahepatic and intracardial) and blood clotting (aorta and intrahepatic venous vessels). Cohen’s Kappa statistics and intraclass correlation coefficient (ICC) were used to evaluate intra- and interobserver agreement. Results Intrahepatic gas was evident after 12, 17 and 30 h. Also, intracardiac gas was present in all animals. However, no chronological appearance has been observed. Blood clotting in the hepatic vein was observed within 3 min, aortic clotting with a delay of 2–12 h after death. Interlobular pulmonary fluid (median PMI: 2 h, range 2–2 h), pleural effusion (median PMI: 10.5 h, range 9-12 h) and hepatic interlobar fissure fluid (median PMI: 11.5 h, range 11–12 h) displayed a chronological appearance pattern. Qualitative and quantitative detection of most postmortem findings showed excellent intra- and interobserver agreement with Kappa values > 0.8 or ICC > 0.75. Conclusion Pulmonary and hepatic fissural fluid collection as well as intravasal gas accumulation are early time-related image findings in postmortem MRI. The chronological appearance of these findings can be assessed with excellent observer agreement in a porcine model. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Campomanesia velutina leaves and branches infusions are used in Brazilian folk medicine to treat diarrhea and to ameliorate intestinal cramps, respectively. Aim of the study Carry out the acute and sub chronic pre-clinical evaluation and thus assess the safety and toxicological potential of the specie. Materials and methods In vivo toxicity was evaluated by acute and sub chronic toxicity assays conducted according to the guidelines of the Brazilian Agency of National Health Surveillance (Agência Nacional de Vigilância Sanitária – ANVISA). For acute toxicity evaluation, a single dose of aqueous extracts from the leaves (AEL) and branches (AEB) of Campomanesia velutina were orally administered to mice at doses of 300, 600 and 1200 mg/kg. Then, the animals were observed for 14 days. In the sub chronic study, the extracts were orally administered to mice for 14 days at doses of 300, 600 and 1200 mg/kg. To assess the toxicological effects, animals were closely observed on general behavior, clinical signs of toxicity, body weight, food and water intake. At the end of the experiment, it was performed biochemical and hematological evaluations, as well as histopathological analysis from the following organs: brain, heart, lungs, liver, stomach, small intestine (section) and left kidney. Preliminary phytochemical analysis was performed using thin layer chromatography (TLC) and colorimetric pharmacognostic tests. Results In oral acute assay, treatment with AEB at the major dose (1200 mg/kg) caused diarrhea, abdominal cramps and tremors in females. These effects were reversed at 4th hour. Normochromic normocytic anemia was observed in males treated with AEL 300 mg/kg and AEB 600 and 1200 mg/kg as well as in females treated with AEB 300 and 1200 mg/kg. The kidney of all treated animals showed moderate inflammation and a few hemorrhagic points. In sub chronic assay, treatment with AEL 600 mg/kg, AEL 1200 mg/kg and AEB 1200 mg/kg caused hyper excitability in females that was not reversed. Treatments also had impact on weight gain and the relative weight of males’ brain was increased on group treated with AEL 300 mg/kg, AEB 300 and AEB 1200 mg/kg. Although changes in hematological parameters were not observed, serum creatinine levels were significantly higher in males treated with AEB 300 mg/kg. Besides, the heart of all treated animals showed intense hyperemia. Preliminary phytochemical analysis revealed the presence of flavonoids, tannins and phenolic compounds. Conclusions Toxicity signs were mainly observed after treatment with AEL and AEB at the two highest tested doses (600 and 1200 mg/kg), suggesting that the extracts are relatively safe at its effective dose (300 mg/kg). However, alterations on hematological and biochemical parameters and on the kidney and heart of the animals were not closely related with the dose, implying caution on its use. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Hwangryunhaedok-tang is an oriental herbal formula treated to cure inflammation and gastric disorders in China, Japan, and Korea. We explored the protective effects of Hwangryunhaedok-tang water extract (HRWE) against airway pathophysiological changes caused by cigarette smoke (CS) and lipopolysaccharide (LPS) in a mouse. Materials and methods We performed quantitative analyses of five marker components, namely geniposide, baicalin, coptisine, plamatine, and berberine, using high-performance liquid chromatography. Animals were received CS exposure (1 h per day) for 7 days. LPS was administered intranasally on day 4. Mice were received HRWE at dose of 100 or 200 mg/kg for 1 h before CS exposure. Results Treatment with HRWE significantly suppressed the increased inflammatory cell count induced by CS and LPS exposure. In addition, reduction in IL-6, TNF-α and IL-1β in broncho-alveolar lavage fluid (BALF) was observed after HRWE treatment. HRWE not only decreased inflammatory cell infiltration in lung, but also decreased the expression of iNOS, NF-κB and matrix metallopeptidase (MMP)-9 in lung tissues. Conclusion This study showed that HRWE can attenuate respiratory inflammation caused by CS and LPS exposure. Therefore, HRWE has potential for treating airway inflammatory disease. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Mandevilla longiflora, popularly known as “velame" in central Brazil, is a subshrub widely distributed in South America. Its xylopodium is used in the form of a decoction or infusion to treat inflammation and other ailments. Aim of the Study This study aimed to evaluate the anti-inflammatory potential of M. longiflora in an in vivo model of ovalbumin-induced immediate hypersensitivity, identifying its effects on leukocyte infiltration, IgE and LTB 4 levels, and Th2 cytokine production. In addition, HPLC fingerprint of the extract was performed. Material and methods The hydroethanolic extract 70% of M. longiflora (HEMI) was obtained by maceration of the plant xylopodium. Swiss mice were sensitized by i.p. injection OVA-aluminium hydroxide on days 1 and 10. Nine days after the last sensitisation animals were challenged for 6 consecutive days with OVA solution for 20 min daily in a closed chamber under continuous flow of aerosol. The animals were treated with HEMl (20, 50 and 200 mg/kg p.o.), 2 times per day, and euthanized 24 h later. Animals treated with vehicle (2% Tween-20) or dexamethasone were used as negative and positive controls, respectively. The recruitment of inflammatory cells into the pulmonary cavity was evaluated by counting cells present in broncho-alveolar lavage fluid (BALF). Lung tissue was also collected for histopathology and infiltration analysis. Quantification of IL-4, IL-5 and IL-13 from the BALF, and IgE, and LTB 4 from plasma, were conducted by immunoassay. Results and conclusions The HEMl attenuated leukocyte migration into the airways, which was evidenced by a decrease in eosinophils, neutrophils and mononuclear cells, both in BALF quantification and by histopathological analysis, as well as decreasing the concentrations of IL-4, IL-5, IL-13, IgE and LTB 4 . All of these events are typical of air-mucosa inflammatory disease. These findings scientifically evidence for the first time the ethnopharmacological use of M. longiflora to treat chronic inflammatory events, such as asthma, and suggest a potential therapeutic use or complementary therapy for this plant extract. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Bergenin, an active constituent of the plants of the genus Bergenia, was reported to have anti-inflammatory effects in the treatment of chronic bronchitis and chronic gastritis clinically. However, its therapeutic effect on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and its potential mechanisms of actions were still unknown. Aim of this study To evaluate the effect of bergenin on murine model of acute lung injury induced by LPS and also to explore its potential mechanisms. Materials and methods Half an hour and 12 h after an intranasal inhalation of LPS, male BALB/c mice were treated with bergenin (50,100 and 200 mg/kg) or dexamethasone (DEX, 5 mg/kg) by gavage. Twenty-four hours after LPS exposure, the lung wet/dry ratio, histological changes, myeloperoxidase (MPO) in lung tissues, inflammatory cells (in BALF) and cytokines (in BALF and serum) were detected. Meanwhile, the protein expression of MyD88 and the phosphorylation of NF-κB p65 in lung tissue were analyzed using immunoblot analysis. Moreover, the nuclear translocation and the phosphorylation of NF-κB p65 in Raw264.7 cells were also analyzed. The viability of Raw264.7 cells was determined by MTT assay. Results Results showed that bergenin significantly decreased pulmonary edema, improved histological changes and reduced MPO activity in lung tissues. Moreover, bergenin obviously decreased inflammatory cells, IL-1β and IL-6 production in BALF, as well as IL-1β, TNF-α and IL-6 production in serum of LPS-induced ALI mice. Furthermore, bergenin markedly inhibited LPS-induced NF-κB p65 phosphorylation, as well as the expression of MyD88 but not the expression of NF-κB p65 in lung tissues. Additionally, bergenin also significantly inhibited the nuclear translocation and the phosphorylation of NF-κB p65 stimulated by LPS in Raw264.7 cells. Conclusions These findings suggested that bergenin had a therapeutic effect on LPS-induced ALI by inhibiting NF-κB activition. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Previous studies showed that Helminthostachys zeylanica (L.) Hook. could reduce inflammatory responses in macrophage and brain astrocytes. Aim of the study In the present study, we evaluated whether an ethyl acetate extract (HZE) or a water extract (HZW) of H. zeylanica could reduce inflammatory responses in lung epithelial cells and ameliorate lipopolysaccharide (LPS)-induced acute lung injury in mice. Methods Human lung epithelial A549 cells were pre-treated with HZE or HZW (1–10 μg/mL), then stimulated with LPS. BALB/c mice received oral HZW for 7 consecutive days, then an intratracheal instillation of LPS to induce lung injury. Results HZW reduced chemokine and proinflammatory cytokine production in LPS-activated A549 cells. HZW also suppressed ICAM-1 expression and reduced the adherence of acute monocytic leukemia cells to inflammatory A549 cells. HZE had less efficacy than HZW in suppressing inflammatory responses in A549 cells. In vivo, HZW significantly suppressed neutrophil infiltration and reduced the TNF-α and IL-6 levels in bronchoalveolar lavage fluid and serum from LPS-treated mice. HZW also modulated superoxide dismutase activity, glutathione, and myeloperoxidase activity in lung tissues from LPS-treated mice. HZW decreased the phosphorylation of mitogen-activated protein kinase and nuclear factor kappa B, and promoted heme oxygenase-1 expression in inflamed lung tissue from LPS-treated mice. Conclusion Our findings suggested that HZW reduced lung injury in mice by reducing oxidative stress and inflammatory responses. HZW also reduced inflammatory responses in human lung epithelial cells. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Eclipta prostrata (L.) L. (Asteraceae) has been used in Brazilian traditional medicine to treat asthma and other respiratory illnesses. Aims of the study To investigate the effects of different doses of a standardized extract of E. prostrata using a murine model of allergen induced asthma. Materials and methods Balb/c mice were sensitized twice with ovalbumin (OVA) administered intraperitoneally and challenged over four alternate days with nasal instillations of OVA solution. The standardized methanol extract of E. prostrata was administered in doses of 100, 250 and 500 mg kg − 1 concomitantly with nasal instillation over seven consecutive days. Control animals were treated with dexamethasone or saline solution. Bronchial hyperresponsiveness, production of Th1 and Th2 cytokines, allergen sensitization, airway and lung inflammation, mucous secretion and airway remodeling were assessed. Results The concentrations of chemical markers in the standardized methanol extract were 0.02% oroboside, 1.69% demethylwedelolactone and 1.71% wedelolactone. Treatment with 250 mg kg −1 of extract, which provided 0.745, 4.22 and 4.30 mg kg − 1 day −1 of oroboside, demethylwedelolactone and wedelolactone, respectively, significantly reduced ( P <0.05) respiratory resistance and elastance. Such effects were comparable with those produced by dexamethasone. The total number of inflammatory cells and eosinophils in the bronchoalveolar lavage and the concentrations of interleukin (IL)-4, IL-5 and IL-13 in lung homogenate were significantly reduced ( P <0.05) by the methanol extract of E. prostrata. Conclusion The results presented herein demonstrate for the first time the anti-inflammatory activity of E. prostrata in a murine model of asthma, thereby supporting the ethnopharmacological uses of the plant. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance The stem bark of Terminalia arjuna (Roxb.) is widely used in Ayurveda in various cardiovascular diseases. Many animal and clinical studies have validated its anti-ischemic, antihypertensive, antihypertrophic and antioxidant effects. Pulmonary hypertension (PH) is a fatal disease which causes right ventricular hypertrophy and right heart failure. Pulmonary vascular smooth muscle hypertrophy and increased oxidative stress are major pathological features of PH. As available limited therapeutic options fail to reduce the mortality associated with PH, alternative areas of therapy are worth exploring for potential drugs, which might be beneficial in PH. Aim of the study The effect of a standardised aqueous extract of the stem bark of Terminalia arjuna (Roxb.) in preventing monocrotaline (MCT)-induced PH in rat was investigated. Materials and methods The study was approved by Institutional Animal Ethics Committe. Male Wistar rats (150–200 g) were randomly distributed into five groups; Control, MCT (50 mg/kg subcutaneously once), sildenafil (175 µg/kg/day three days after MCT for 25 days), and Arjuna extract (TA125 and TA250 mg/kg/day orally after MCT for 25 days). PH was confirmed by right ventricular weight to left ventricular plus septum weight (Fulton index), right ventricular systolic pressure (RVSP), echocardiography, percentage medial wall thickness of pulmonary arteries (%MWT). Oxidative stress in lung was assessed by super oxide dismutase (SOD), catalase, reduced glutathione (GSH) and thiobarbituric acid reactive substance (TBARS). The protein expressions of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX-1) in lung and gene expression of Bcl2 and Bax in heart were analyzed by Western blot and RT PCR respectively. Results MCT caused right ventricular hypertrophy (0.58±0.05 vs 0.31±0.05; P<0.001 vs. control) and increase in RVSP (33.5±1.5 vs 22.3±4.7 mm of Hg; P<0.001). Both sildenafil and Arjuna prevented hypertrophy and RVSP. Pulmonary artery acceleration time to ejection time ratio in echocardiography was decreased in PH rats (0.49±0.05 vs 0.32±0.06; P<0.001) which was prevented by sildenafil (0.44±0.06; P<0.01) and TA250 (0.45±0.06; P<0.01). % MWT of pulmonary arteries was increased in PH and was prevented by TA250. Increase in TBARS (132.7±18.4 vs 18.8±1.6 nmol/mg protein; P<0.001) and decrease in SOD (58.4±14.1 vs 117.4±26.9 U/mg protein; P<0.001) and catalase (0.30±0.05 vs 0.75±0.31 U/mg protein; P<0.001) were observed in lung tissue of PH rats, which were prevented by sildenafil and both the doses of Arjuna extract. Protein expression of NOX1 was significantly increased in lung and gene expression of Bcl2/Bax ratio was significantly decreased in right ventricle in MCT-induced PH, both were significantly prevented by Arjuna and sildenafil. Conclusions Aqueous extract of Terminalia arjuna prevented MCT-induced pulmonary hypertension which may be attributed to its antioxidant as well as its effects on pulmonary arteriolar wall thickening. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance The traditional Chinese medicine Niubeixiaohe (NBXH) is an effective anti-tuberculosis prescription, which is made up of Bulbus Fritillariae Cirrhosae, Rhizoma Bletillae , Radix Platycodonis , Fructus Arctii , Herba Houttuyniae and Glutinous rice. In this study, NBXH powder (I) and three kinds of NBXH extracts (II, III, and IV) were prepared. The water decoction of NBXH had been used to treat TB in clinic sixteen years suggested that it was effective to treat TB. Aim of the study This study evaluated the effects of different processing products of NBXH on mouse TB model in vivo and provide a new Chinese medicine for the clinical treatment of TB. Materials and methods In this study, 120 female BALB/c mice infected with Mycobacterium tuberculosis H37Rv, were treated with distilled water, M. vaccae vaccine, the low, middle and high doses of NBXH I, the low, middle and high doses of NBXH II, the low, middle and high doses of NBXH III, the low, middle and high doses of NBXH IV for 12 weeks, respectively. Results The body weights of mice in all NBXH groups were higher than that in the water group. The weight indexes of the spleens in M. vaccae group, the middle dose of NBXH II group, the low dose of NBXH IV group and in the high dose of NBXH IV group were significantly lower than that in the water group( P <0.05). Compared with the water group, the spleen colony counts in the low dose of NBXH I group, the high dose of NBXH II group, the low dose of NBXH III group and the high dose of NBXH IV group reduced by 0.43, 0.46, 0.73, 0.58 logs ( P <0.05), respectively. But the lung colony counts had no significant difference between each group. Pulmonary general pathology and histopathology displayed that the lung lesions in treatment groups were improved at certain degree, especially in the low dose of NBXH IIIand IV groups, in which their areas of the lesions were less than 50%, and the half normal lung structure in half of the mice could be observed. Conclusion Powder and three extracts of traditional Chinese medicine NBXH all had anti-tuberculosis therapeutic effects on mouse tuberculosis model, and this study provided a base for the further development of Chinese patent medicine NBXH. Also, this is the first report on comprehensive experimental research of NBXH extracts coming from six kinds of traditional Chinese medicine. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Selaginella uncinata (Desv.) Spring, known as “Cuiyuncao”, is a perennial herb widely distributed in the Southeast Asian countries. In the folk medicine, the local minority commonly use it to treat cough and asthma for centuries. Aim of the study This study was carried out to investigate the protective mechanisms of total flavonoids from S. uncinata (SUF) on airway hyperresponsiveness, cytokine release and bitter taste receptors (T2Rs) signaling with emphasis on inflammatory responses in a rat model of ovalbumin (OVA)-induced asthma. Materials and methods Rats were sensitized and challenged with OVA to induce typical asthmatic reactions. Pathological changes of lung tissue were examined by HE staining. The serum levels of T cell-associated cytokines (IFN-γ, IL-4, IL-5 and IL-13), total IgE and OVA-specific IgE were determined by enzyme-linked immunosorbent assay (ELISA). Gene expressions of T2R10, IP3R1 and Orai1 in lung tissue were assayed by fluorescence quantitative real-time polymerase chain reaction (FQ-PCR) while protein expressions of NFAT1 and c-Myc were assayed by western blot analysis. The activation of SUF was investigated on tansgentic T2R10-GFP HEK293 cells. Results SUF treatment attenuated airway hyperresponsiveness and goblet cell hyperplasia compared with OVA-challenged asthmatic rats. The serum levels of IL-4, IL-5 and IL-13 as well as total and OVA-specific IgE were decreased while serum IFN-γ was increased in SUF-treated rats. SUF treatment significantly up-regulated T2R10 gene expression, down-regulated IP3R1 and Orai1 gene expression. SUF further suppressed eotaxin, NFAT1 and c-Myc protein expression in lung tissues of OVA-challenged rats. Conclusions These results imply that SUF exerts anti-inflammatory function through the T2R10/IP3R1/NFAT1 dependent signaling pathway, and may warrant further evaluation as a possible agent for the treatment of asthma. [ABSTRACT FROM AUTHOR]

Purpose Determine the ability of quantitative CT (QCT) in defining parenchymal density changes in acute pulmonary embolism (PE). Material & methods Mean lung density (MLD) and percentage distribution values (PDV) were calculated in 34 patients suspected of PE using software application based on computerized volumetric anatomical segmentation. Results Total, left, and right MLD differed significantly between emboli positive(n = 23) and negative(n = 11) groups( p < 0.006, p < 0.009, p < 0.014). PDVs differed between groups ( p < 0.05) except for LUZ and RLZ. When PE was present in lobe &/segment branches, PDVs were significantly lower except RUZ. Conclusion QCT is a promising application for defining parenchymal density changes in PE revealing potential functional impact of emboli. This preliminary study suggests QCT could provide added value to CTPA in peripheral PE. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance A standardized bark extract of Pinus pinaster Aiton (Pycnogenol ® ; PYC) used as an herbal medicine to treat various diseases in Europe and North America. Aim of the study This study evaluates the ability of PYC to inhibit chronic obstructive pulmonary disease (COPD) in the cigarette smoke extract (CSE)-stimulated human airway epithelial cell line NCI-H292 and in a cigarette smoke (CS) and lipopolysaccharide (LPS)-induced mouse model. Methods To induce COPD, the mice intranasally received LPS on day 4 and were exposed to CS for 1 h per day (total eight cigarettes per day) from days 1–7. The mice were administered PYC at a dose of 15 mg/kg and 30 mg/kg 1 h before CS exposure. Results In the CSE-stimulated NCI-H292 cells, PYC significantly inhibited Erk phosphorylation, sp1 expression, MUC5AC, and pro-inflammatory cytokines in a concentration-dependent manner, as evidenced by a reduction in their mRNA levels. Co-treatment with PYC and Erk inhibitors markedly reduced the levels inflammatory mediators compared to only PYC-treatment. In the COPD mice model, PYC decreased the inflammatory cell count and the levels of pro-inflammatory cytokines in the broncho-alveolar lavage fluid compared with COPD mice. PYC attenuated the recruitment of inflammatory cells in the airways and decreased the expression levels of Erk phosphorylation and sp1. PYC also inhibited the expression of myeloperoxidase and matrix metalloproteinases-9 in lung tissue. Conclusion Our results indicate that PYC inhibited the reduction in the inflammatory response in CSE-stimulated NCI-H292 cells and the COPD mouse model via the Erk-sp1 pathway. Therefore, we suggest that PYC has the potential to treat COPD. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Tongxinluo (TXL), which is a Chinese medicine rooted from traditional used herbs, has been used in clinic to treat cardiovascular and cerebrovascular diseases. However, it remains unknown whether TXL alleviates low pressure hypoxic pulmonary hypertension. Aim of the study Here, we aimed to observe the influence of TXL on pulmonary hypertension in a rat model that exposed to high altitude environment characterized by low pressure hypoxia. Materials and methods A total of 32 male Sprague-Dawley rats were divided into four groups: control group (normal pressure and normoxia), pulmonary hypertension group (PAH, the parameter is equal to that in altitude 5000 m), TXL group (rats living in environment equal to that at altitude of 5000 m received TXL treatment), vardenafil group (VDNF, rats living in environment equal to that altitude of 5000 m received vardenafil treatment). The high altitude environment was created in chamber by adjusting the inner pressure and oxygen content concomitantly. Before entering the chamber, the TXL group was given TXL (1.2 g kg −1 d −1 ) for 28 days, and the VDNF group was given VDNF (0.1 g kg −1 d −1 ) for 28 days. After 28 days, the mean pulmonary artery pressure (mPAP) and right ventricular pressure was measured using right heart catheterization. The weight of the right ventricle (RV), left ventricle (LV) and interventricular septum (IVS) was measured, and the right ventricular mass index was calculated. Lung tissue was subjected to hematoxylin and elastic fiber staining, and the medial wall thickness (MT), medial wall cross-sectional area (MA), MT%, and MA% were measured. Proliferative activity within the pulmonary arteries was quantified by Ki67staining. Results After 28 days, as compared with that in normal control group, animals living in the chamber (PAH group) showed a significant increase in mPAP( 47.5 mmHg versus 18 mmHg), RV/LV+IVS (0.45 versus 0.21) and MA% (78% versus 44%), respectively. Administration of TXL resulted in a significant decrease of 20 mmHg in mPAP, returning of RV/LV+IVS to 0.27, and a 40% reduction in MT% compared with that in PAH group. In the VDNF group, RV/LV+IVS and MT% was 0.268 and 38.77, significantly lower than that in PAH group. While, mPAP increased by 12.5 mmHg with treatment by VDNF. In contrast to the PAH group, alpha- Smooth Muscle Actin (α-SMA reduced by 19% in the TXL group (p=0.005) and 16% in the VDNF group (p=0.01). Ki67 expression in the VDNF group was significantly lower than the PAH group (P<0.01). Ki67 expression in the TXL group was significantly lower than the PAH group (P<0.01). Compared with the VDNF group, the indexes above reduced in the TXL group. Our results indicate that TXL significantly reduces pulmonary artery pressure, right ventricular hypertrophy, pulmonary small artery wall thickness, and luminal stenosis. In addition, smooth muscle proliferation markedly decreased and muscular artery decreased. However, TXL was unable to restore parameters to control levels. Conclusions The automatic-adjusted low pressure hypoxic chamber was capable of establishing a pulmonary hypertension rat model at an altitude of 5000 m. Compared with VDNF, TXL decreased mPAP and right ventricular hypertrophy index (RVHI) in the pulmonary hypertension rat model, and prevented vascular remodeling by reducing small pulmonary artery thickening, smooth muscle thickening and proliferation. Thus, TXL may be a potential treatment for pulmonary hypertension. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance The leaves of Syzygium cumini (L.) or Skeels (Myrtaceae) are widely used in Brazilian folk medicine to treat diabetes. Aim of the study The present study evaluated the functional capacity, biochemical parameters, oxidative stress and DNA damage from eight weeks of intervention with a crude hydroalcoholic extract of S. cumini leaves (EBH) and continuous aerobic training (TAC) in diabetic (D) rats. Materials and methods A hydroalcoholic (50%) extract was prepared by ultrasound and phytochemical parameters (total phenols, total tannins and myricetin content) were analyzed. Thirty-seven male Wistar rats were divided into five groups: normoglycemic controls (CONT), diabetic controls (D-CONT), diabetics treated with extract (D+EBH), trained diabetic (D+TAC) and diabetics treated with extract and trained (D+EBH+TAC). Functional capacity was assessed with a maximum exercise capacity test; biochemical parameters with enzymatic kits; oxidative stress by superoxide dismutase (SOD), catalase (CAT), thiobarbituric acid reactive substances (TBARS) and oxidized dichlorofluorescein (DCF), and the DNA damage by the comet assay. Results The D+TAC and D+EBH+TAC groups showed better functional capacity at the end of interventions. The D+EBH group showed glucose and triglyceride reduction, lowest DNA damage index in the blood, liver, kidney, heart, lung and gastrocnemius muscle, improved SOD levels in the liver, kidney and lung, improved CAT levels in the kidney and lower lipid peroxidation in all tissues studied, compared to the D-CONT group. The exercise (D+TAC) was effective in reducing triglycerides, improving SOD levels in the lung, reducing lipid peroxidation in all tissues studied and reducing the DCF oxidation in the kidney, in addition to protecting against DNA damage in the blood and heart. However, the additive effect of the intervention protocols when combined (EBH+TAC) was observed only in improving the gastrocnemius SOD levels. The phytochemical analyses showed a high content of phenols and the presence of myricetin glycosides. Conclusion The findings in this study suggest a crude hydroalcoholic extract of S. cumini leaves has potential hypoglycemic, hypolipidemic and protective properties acting against oxidative stress and against DNA damage, probably due to its phenols and myricetin glycoside content and the antioxidant properties of these constituents. Moreover, exercise was suggested to have beneficial effects on diabetes, improving functional capacity, ameliorating blood triglyceride control and decreasing lipid peroxidation, but with no effects on ameliorating blood glucose levels. The association of intervention protocols presented an additive effect on the antioxidant SOD activity in the muscle cells of diabetic rats. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Schizonepeta tenuifolia Briq. (ST) herbs have been used as a Traditional Chinese Medicine (TCM) for treating colds for thousands of years. The volatile oil is considered as the main material basis responsible for the efficacy of ST and has attracted lots of attention on its anti-inflammatory effect recently. Aim of study This paper investigated the anti-inflammatory effects of the distilled volatile oils from Schizonepeta tenuifolia (STVO) that were collected at different harvesting times on carrageenin-induced pleurisy in rats. Based on the anti-inflammatory effects, instead of contents of marker components, we aim to evaluate the quality and determine the appropriate harvesting time of ST. Materials and methods There were eleven groups with eight male rats in each randomly. They were model group, control group, positive group (dexamethasone) and eight groups treated with eight STVOs at different harvesting times. All treatments were performed by gavage and administered once a day on four consecutive days. One hour after the last treatments, except the rats in control group, those in other groups were treated with carrageenin to induce the pleurisy. Four hours later, all the rats were sacrificed and their pleurisy exudates and lung tissues were collected for further analysis. To evaluate the comprehensive anti-inflammatory effect of the eight STVOs, multi-attribute comprehensive index method (MACIM) was used to obtain the integration of various effects. Results All the eight STVOs could decrease the seven indicators relating to pleurisy, which were exudate volume, leukocytes, protein level, myeloperoxidase (MPO), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α) and interleukine-1β (IL-1β). Majority of these decreases were significant (P<0.01, P<0.05). As far as each indicator was concerned, each STVO showed different effect from others. With MACIM, it was found that STVO in Group 6 was the most effective one with the highest V s and appropriate harvesting time of ST was in late September. Conclusions The study may provide scientific basis to further understanding of the mechanism of STVO in anti-inflammatory effect of carrageenin-induced pleurisy. Meanwhile, this study also provides a new access to determining the appropriate harvesting time of TCM and even evaluating the quality of TCM. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Bulb of Fritillaria cirrhosa D.Don (BFC) has been wildly used in China for a long time for folk medicine since its significant therapeutic effects on respiratory diseases, such as cough, expectoration, pneumonia and bronchial inflammation, which are related to respiratory inflammatory response. However, there is a lack of investigation on the in vivo anti-inflammatory properties of BFC. Aim of the study The aim of this study was to evaluate the in vivo anti-inflammatory activity of the purified total alkaloid fraction of BFC (TAF) by using different animal models of inflammation to provide scientific evidence for its traditional use. Materials and methods The total alkaloid fraction from BFC was prepared by using H-103 resin column. Anti-inflammatory effect of TAF was evaluated by models of acetic acid-induced capillary permeability accentuation, carrageenan-induced rat paw edema, cotton pellet-induced granuloma formation and LPS-induced acute lung injury (ALI). The level of cytokines (TNF, IL-6, IL-4 and IL-10) was measured by ELISA. Histopathological analyses were performed by using hematoxylin and eosin staining. Results TAF can inhibit acetic acid-induced capillary permeability accentuation, carrageenan-induced paw edema, cotton pellet-induced granuloma formation, suppress inflammatory cells recruitment and cytokine production in the bronchoalveolar lavage fluid from LPS-induced ALI mice, and attenuate pathological changes in the lung tissues of ALI mice. Conclusion This study provides scientific evidence for bulb of F. cirrhosa to treat respiratory inflammation. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Traditional Chinese medicine (TCM) is clinically used under the guidance of its unique theory system. Bufei Yishen (BY) granules, an oral Chinese herbal formula, is confirmed effective for treating the syndrome of lung-kidney qi deficiency in chronic obstructive pulmonary disease (COPD) patients. Shu-Fei Tie ointment is another prescription for acupoint sticking (AS) therapy based on the theory of treating an internal disease by external treatment on proper acupoints. The beneficial effects of BY granules combined with Shu-Fei Tie have been proved in previous clinical trials. However, the underlying mechanism remains unclear. The present study was initiated to explore the antioxidative mechanism of the integrated therapy of BY granules and acupoint sticking via regulating by peroxisome proliferator activated receptor-gamma (PPARγ) signaling in a cigarette-smoke/bacterial exposure induced COPD rat model. Materials and methods Rats were randomized into Control, Model, BY, AS, BY+AS and aminophylline (APL) groups. COPD rats were induced by cigarette-smoke and bacterial exposures, and were administrated with normal saline, BY granules, AS, BY+AS or aminophylline from week 9 and sacrificed at week 20. Activity of superoxide dismutase (SOD) and levels of methane dicarboxylic aldehyde (MDA) in peripheral blood and bronchoalveolar lavage fluid (BALF) were determined by hydroxylamine and thiobarbituric acid methods. The gene and protein expressions of PPARγ in the lung tissues were analyzed by quantitative polymerase chain reaction and western blot. Results Serum and BALF SOD decreased significantly in Model group ( P <0.01), while MDA increased ( P <0.01). Compared to COPD rats, serum SOD was higher in all treatment groups ( P <0.01), and BALF SOD was higher in BY and BY+AS groups ( P <0.01); serum and BALF MDA was lower in all treatment groups ( P <0.01). Serum and BALF SOD was higher in BY+AS group than in AS group, while MDA was lower ( P <0.05). BALF SOD increased in BY+AS group compared with APL group, while MDA decreased ( P <0.05). PPARγ mRNA and protein and the phosphorylation of PPARγ (p-PPARγ) decreased in COPD rats ( P <0.01), and increased in all treatment groups ( P <0.01). PPARγ mRNA was higher in BY+AS group than in AS group ( P <0.05), PPARγ and p-PPARγ were higher in BY+AS group than in AS and APL groups ( P <0.05, P <0.01); P P ARγ protein was higher in BY group than in APL group ( P <0.05). Conclusion Bufei Yishen granules, Shu-Fei Tie and their combination have beneficial effects in stable COPD, and can attenuate the oxidative stress, and the activation of PPARγ signaling might be involved in the underlying mechanisms, but there are no obvious synergistic effect of Bufei Yishen granules and Shu-Fei Tie. [ABSTRACT FROM AUTHOR]

The aim of this prospective observational study was to evaluate the performance of lung ultrasound (LUS) in detecting post-operative atelectasis in adult patients under general anesthesia. Forty-six patients without pulmonary comorbidities who were scheduled for elective neurosurgery were enrolled in the study. A total of 552 pairs of LUS clips and thoracic computed tomography (CT) images were ultimately analyzed to determine the presence of atelectasis in 12 prescribed lung regions. The accuracy of LUS in detecting peri-operative atelectasis was evaluated with thoracic CT as gold standard. Levels of agreement between the two observers for LUS and the two observers for thoracic CT were analyzed using the κ reliability test. The quantitative correlation between LUS scores of aeration and the volumetric data of atelectasis in thoracic CT were further evaluated. LUS had reliable performance in post-operative atelectasis, with a sensitivity of 87.7%, specificity of 92.1% and diagnostic accuracy of 90.8%. The levels of agreement between the two observers for LUS and for thoracic CT were both satisfactory, with κ coefficients of 0.87 (p < 0.0001) and 0.93 (p < 0.0001), respectively. In patients in the supine position, LUS scores were highly correlated with the atelectasis volume of CT (r = 0.58, p < 0.0001). Thus, LUS provides a fast, reliable and radiation-free method to identify peri-operative atelectasis in adults. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Mahuang-Xixin-Fuzi Decoction (MXF) as a famous formula for the treatment of colds, fever, nasal congestion and headache with elder people, has always been widely used in traditional Chinese medicine. The present study is aimed at investigating the treatment effect of MXF on Kidney-Yang deficiency syndrome in mice simultaneously infected with H1N1 virus. Materials and methods We employed the Kidney-Yang deficiency mouse model to investigate the effect of MXF against influenza A virus (A/FM/1/47, H1N1). Mice were infected with the virus after fifteen days Kidney-Yang deficiency syndrome was established (intraperitoneal injection of estradiol benzoate), while MXF was orally administrated with 1.2–4.7 g/kg/d for 6 consecutive days after inoculation. Body weight, rectal temperature, morbidity, and mortality were recorded daily. Histopathologic changes, antioxidant activity of SOD and MDA were detected. Moreover, levels of inflammatory cytokines including IL-6, IL-10, MCP-1, TNF-α were measured in the sera of mice. Results We found that the extract of MXF at dosages of 2.3–4.7 g/kg could effectively diminish mortality rate, ameliorate lung edema and inflammation. Administration of MXF decoction significantly depressed the expression of IL-6, MCP-1 and TNF-α, and markedly increased expression of IL-10 in serum. Simultaneously, the extract was also found to reduce MDA and increase SOD in the lung tissue of mice. Conclusion These data support the notion that the extract of MXF could treat Kidney-Yang deficiency syndrome in mice simultaneously infected with influenza A virus by reducing inflammation and increasing antioxidant activities. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Mahaenggamseok-tang (MHGST), an herbal formula in traditional Asian medicine, has been used to treat patients with various pulmonary diseases including common cold and influenza. However, the potential therapeutic effect of MHGST on acute lung injury (ALI), a leading cause of death worldwide, and the anti-inflammatory mechanisms of MHGST remained less understood. Materials and methods The methanol extract of MHGST was prepared and fingerprinted by HPLC. For the induction of ALI, C57BL/6 mice (n=5/group) received a single intraperitoneal (i.p.) injection of LPS. Referring to the dose for patients, two different amounts of MHGST were delivered in an aerosol to mouse lungs via trachea 2 h after the i.p. LPS administration. Lung histology, bronchoalveolar lavage fluid, myeloperoxidase (MPO) activity, and the expression of inflammatory and Nrf2-dependent genes were analyzed to determine the effect of MHGST on lung inflammation. For mechanistic studies, western blotting and semi-quantitative RT-PCR were conducted using RAW 264.7 cells. Results When administered 2 h after the onset of ALI, MHGST relieved lung pathology characteristic to ALI, with decreases of neutrophil infiltration and MPO activity. While suppressing the expression of inflammatory genes, MHGST increased the expression of Nrf2-dependent genes in ALI mouse lungs. Concordantly, MHGST activated Nrf2 activity while suppressing NF-κB in RAW 264.7 cells. Conclusion MHGST suppressed neutrophilic lung inflammation, a hallmark of ALI, which was associated with the activation of anti-inflammatory Nrf2 and the suppression of pro-inflammatory NF-κB. Our results suggest that MHGST has a therapeutic potential against ALI. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Morinda citrifolia L. (Noni) is a medicinal plant used in Polynesia for many properties such as anti-inflammatory, anti-diabetic and antineoplastic effects. Recent studies showed that noni juice have anti-oxidant and acute anti-inflammatory activities likely due to polyphenols, iridoids and vitamin C content. The present study was undertaken to evaluate chronic anti-inflammatory and spasmolytic effects of noni juice. Materials and methods Therefore, we evaluated the effect of oral or intraperitoneal administrations of noni juice in vivo on the lung inflammation in ovalbumin (OVA) sensitized Brown Norway rat (with prednisolone 10 mg/kg intraperitoneously as reference compound) and the ex vivo effect of noni juice on BaCl 2 (calcium signal) or methacholine (cholinergic signal) induced spasms in jejunum segments. Results We found that noni juice (intraperitoneously 2.17 mL/kg and orally 4.55 mL/kg) reduced the inflammation in OVA-sensitized Brown Norway rat with regard to the decreased number of inflammatory cells in lung (macrophages minus 20–26%, lymphocytes minus 58–34%, eosinophils minus 53–30%, neutrophils minus 70–28% respectively). Noni juice demonstrated a dose-dependent NO scavenging effect up to 8.1 nmol of nitrites for 50 µL of noni juice. In addition noni juice inhibited (up to 90%) calcium and cholinergic induced spasms on the jejunum segments model with a rightward shift of the concentration response curve. Conclusion We describe for the first time that noni juice demonstrate (1) a chronic anti-inflammatory activity on sensitized lungs along with (2) a spasmolytic effect integrating a calcium channel blocker activity component. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance In recent years, asthma has increased dramatically in prevalence with a considerable economic burden all over the world. Long-term remission should be regarded as the promising and meaningful therapeutic goal in asthma management. However, the precise definition criteria and rational therapies for asthma remission have not been well-established. In academia, there is a consensus that even in those who develop asymptomatic remission of asthma, persistent airway inflammation is ubiquitous. Gubenfangxiao decoction (GBFXD) has been widely used in treating asthma remission stage for decades in the Jiangsu Province Hospital of Chinese Medicine, China. We previously demonstrated that GBFXD could downregulate the asthma susceptibility gene ORMDL3 , a trigger of Endoplasmic reticulum (ER) stress and unfolded protein response (UPR). Aim this study To investigate the involvement of ER stress and UPR in the anti-inflammatory effects of GBFXD in Respiratory Syncytial Virus (RSV)-OVA-induced asthma remission mice. Materials and methods Mice were orally administered GBFXD at three doses for 30 days after an RSV-OVA challenge. The levels of inflammation mediators in serum were measured using a Luminex assay and the amount of IFN-γ in lung homogenates was detected using ELISA. The splenic CD4+ and CD8+ T lymphocytes were counted using flow cytometric analysis. The mRNA and protein levels of asthma susceptibility gene ORMDL3, ER stress markers (BIP, CHOP), and three canonical UPR branches (PERK-eIF2a-ATF4, IRE1α-XBP1/IRE1α-JNK-AP1 and ATF6-SERCA2b signal pathways) were detected using real-time RT-PCR and western blot. Results Histopathological analysis showed that the model group mice still exhibited a sustained airway inflammation even after suspending the OVA-challenge and RSV infections for 30 days. H&E staining results indicated that GBFXD could attenuate sustained airway inflammation. Decreased serum CXCL1 level and increased IFN-γ level in lung homogenate were observed after GBFXD treatment. Reductions in the number of splenic CD4+/CD8+ T lymphocytes were found after DEX treatment. We further confirmed the previous finding that GBFXD could downregulate the expression of ORMDL3 . As a result of suppressed UPR, decreased ER stress markers and inhibited UPR branches (PERK and IRE1α signal pathway) were also observed through the significant reduction of signature mRNA and protein expressions after GBFXD treatment. Conclusion GBFXD can significantly attenuate RSV-OVA-induced persistent airway inflammation in murine asthma remission model. These effects may be mediated, at least partially, by inhibiting the activation of ER stress responses. [ABSTRACT FROM AUTHOR]

The molecular analysis of pigs vaccinated with a mutant transferrin-binding protein B (Y167A) from Haemophilus parasuis was compared with that performed for unvaccinated challenged (UNCH) and unvaccinated unchallenged (UNUN) pigs. Microarray analysis revealed that UNCH group showed the most distinct expression profile for immune response genes, mainly for those genes involved in inflammation or immune cell trafficking. This fact was confirmed by real-time PCR, in which the greatest level of differential expression from this group were CD14 , CD163 , IL-8 and IL-12 . In Y167A group, overexpressed genes included MAP3K8 , CD14 , IL-12 and CD163 . Proteomics revealed that collagen α-1 and peroxiredoxins 2 and 6 were overexpressed in Y167A pigs. Our study reveals new data on genes and proteins involved in H. parasuis infection and several candidates of resistance to infection that are induced by Y167A vaccine. The expression of proinflammatory molecules from Y176A pigs is similar to their expression in UNUN pigs. [ABSTRACT FROM AUTHOR]

Ethanopharmacological relevance Ecliptae Herba, a nourishing traditional Chinese medicine, is also a folk medicine for the treatment of lung diseases. Aim of the study To investigate the anti-fibrosis effects and the underlying mechanism of the extract of Ecliptae Herba and its potential active components. Materials and methods The resulting extract (EXT) was prepared from the 80% ethanol extract of Ecliptae Herba. After intratracheally administrated with bleomycin (BLM, 5 mg/kg), mice were orally treated with EXT at 2.5, 1.25, 0.625 g/kg and eclipta saponin A (ESA) at 80 mg/kg once daily for 28 day. The bodyweight, survival rate, pathological changes of lung and levels of hydroxyproline (HYP) were used to evaluate the anti-fibrotic effects. The malonaldehyde (MDA), superoxidae dismutase (SOD) activity, and the protein expressions of matrix metalloproteinase (MMP)-2, 9, tissue inhibitor of metalloproteinase-1 (TIMP-1), cyclooxygenase-2 (COX-2), α-smooth muscle actin (α-SMA) and transforming growth factor-β1 (TGF-β1) in lung tissue were analyzed by kits or western blot. Results Compared with BLM group, EXT administration could significantly ameliorated the pathological changes of lung, decreased the HYP content, enhanced the SOD activity, and reduced the MDA content of lung tissues. In mechanism, EXT significantly alleviated the levels of COX-2, TGF-β1, MMP-2 and α-SMA, as well as elevated the ratio value of MMP-9/TIMP-1. Additionally, the anti-fibrosis effects of ESA, a large amount of saponins isolated from Eclipta prostrata , was also evaluated by the BLM-induced model. The results showed that ESA could block BLM-induced histological changes of lung tissue and decrease the high levels of TGF-β1 and α-SMA. Conclusions Ecliptae Herba has protective effects against the pulmonary fibrosis induced by BLM via reducing the oxidative stress, lung tissue inflammation, and the subsequent epithelial–mesenchymal transition. The active chemical constituents may be involved with triterpenoid saponins, such as ESA. [ABSTRACT FROM AUTHOR]

Background: An isomer of the non-psychoactive cannabinoid Δ(9)-THCCOOH was recently detected in blood from cannabis users. The structure of this compound is currently unknown. Therefore, further investigations were performed to elucidate its nature.Methods: Further biological specimens were analyzed using the previously published LC-MS/MS method to evaluate the distribution of this compound in the human body. Hypothetically, the unknown compound was isomeric in the position of the double bond, i.e. Δ(8)-THCCOOH. An in-vitro metabolism study on Δ(8)-THC and Δ(9)-THC was performed to compare the resulting metabolites with the unknown compound.Results: The unknown THCCOOH isomer was detected in all analyzed human body compartments (urine, bile, liver, lung and kidney) except for brain indicating that its detectability is not limited to blood. The in-vitro metabolism assay with the human CYP2C9 isoform led to the formation of THCOH and THCCOOH of Δ(8)-THC and Δ(9)-THC. However, the unknown isomer present in blood exhibited a different retention time than each of the metabolites formed.Conclusion: The unknown THCCOOH isomer accompanied THCCOOH and was detected in various human body compartments. The present in-vitro metabolism study proved that it is not of Δ(8)-THCCOOH structure nor that it is metabolically formed by the human CYP2C9 isoform. [ABSTRACT FROM AUTHOR]

Rhaponticum uniflorum (L.) DC is a member of the Compositae family. Loulu flowers (LLF) is the inflorescence of this plant, which is a commonly used Mongolian medicine for the treatment of inflammatory diseases due to its heat-clearing and detoxifying properties. It is used caused by. However, its anti-inflammatory mechanisms are not clear. Aim of this study : We investigated whether ethanol extracts of LLF can alleviate LPS-induced acute lung injury and explored the mechanism involved. BALB/C mice were intragastrically administered with sodium carboxymethyl cellulose (0.5%, 1 mL/100 g) or ethanol extracts of LLF at a dose of 100, 200, and 400 mg/kg, once daily, for 3 days. Subsequently, mice models of acute lung injury were established by LPS and used for the determination of anti-inflammatory effects of LLF. After 6 h of treatment, mice were sacrificed to collect lung tissues and bronchoalveolar lavage fluid (BALF). H&E staining assay was performed on the tissues for pathological analysis. The ELISA test was conducted to measure NO, IL-6, TNF-α, MPO, SOD, CAT, MDA and GSH-PX levels. The expression level of proteins associated with the Nrf2/HO-1 and MAPK/NF-κB signaling pathways were determined using Western blot analysis. Levels of F4/80 and Nrf2 in lungs were quantified using immunohistochemistry. Oral administration of LLF extracts alleviated LPS-induced pathological alterations, reduced lung W/D weight ratio, decreased levels of TP, pro-inflammatory factors (TNF-α and IL-6), and NO in BALF. Pretreatment with LLF extract downregulated F4/80 expression in lung tissue and suppressed LPS-induced elevations in BALF and lung tissue levels of MPO. Moreover, treatment with LLF extract reduced the expression level of proteins associated with the MAPK signaling pathway (p-p38, p-JNK, p-ERK) and TLR4/NF-κB signaling pathways (TLR4, Myd88, p-IκB, p-p65). Moreover, LLF extract upregulated Nrf2, HO-1 and NQO1 protein levels, downregulated Keap1 protein level. Immunohistochemical analysis revealed that LLF reduced the LPS-induced increase in Nfr2 expression in lung tissues. Ethanol extracts of LLF ameliorated LPS-induced acute lung injury by suppressing inflammatory response and enhancing antioxidation capacity, which correlated with the MAPK/NF-κB and Nfr2/HO-1 signaling pathways. [Display omitted] • LLF showed protective effects on LPS-induced acute lung injury (ALI). • The protective effects of LLF on LPS-induced ALI are associated with inhibited NF-κB and MAPK signaling pathway. • LLF attenuates LPS-induced ALI by promoting the antioxidant capacity through regulating the Nrf2/HO-1 signaling pathway. [ABSTRACT FROM AUTHOR]

Mume Fructus (MF) is a well-known traditional Chinese medicine used to treat chronic cough, prolonged diarrhea, and other inflammation-related diseases. We previously confirmed the anti-colitis effect of its ethanol extract on a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced Crohn's disease (CD) rat model. However, the active ingredien t s and underlying mechanisms of MF remain unknown. To clarify the material basis and potential mechanism of the ethanol extract of MF (MFE) in alleviating CD and its complications, such as lung injury and intestinal obstruction. MF was extracted with 80% ethanol aqueous solution and separated with 0, 40, and 100% ethanol aqueous solutions. MFE and its fractions were screened in a TNBS-induced CD rat model. For the bioactive fraction, the chemical composition was identified and quantified using ultrahigh-performance liquid chromatography coupled with diode-array detection and quadrupole time-of-flight tandem mass spectrometry. Interleukin (IL)-1 β , IL-6, IL-17, transforming growth factor (TGF)- β , and lipopolysaccharide (LPS) levels in the colon, lungs, and/or plasma were detected using enzyme-linked immunosorbent assays. The expression levels of zonula occludens-1 (ZO-1) and occludin in the colon were measured using immunohistochemical staining, and the intestinal microbiota and short-chain fatty acid (SCFA) levels were analyzed using 16S rRNA gene sequencing and gas chromatography/mass spectrometry. The 40% ethanol fraction of MF (MFE40), which mainly contained methyl citrate, ethyl citrate, and caffeoylquinic acid ethyl esters, was identified as the active fraction that could alleviate CD in rats. MFE40 could ameliorate inflammation and fibrosis in the colon and lung tissues by inhibiting the secretion of cytokines, such as IL-1 β , IL-6, IL-17, and TGF- β , along with intestinal obstruction and lung injury in CD rats. The possible mechanisms of MFE40 were related to increased expression of ZO-1 and occludin in the colon, reduction in plasma LPS levels, and restoration of SCFAs via reduction in the relative abundance of Adlercreutzia , Clostridium_sensu_stricto_1 , Erysipelatoclostridium , Faecalibaculum , norank_f_Erysipelotrichaceae , Phascolarctobacterium Coriobacteriaceae_UGG_002 , and Allobaculum and increase in the relative abundance of Escherichia shigella , Christensenella, Acetivibrio_ethanolgignens , and Butyricicoccus. MFE40 had no significant influence on the inflammatory factors in healthy rats. Citrate esters and hydroxycinnamate esters are the main active constituents of MFE40. MFE40 exhibited a remission effect on CD rats and inhibited intestinal obstruction and lung injury via anti-inflammatory effects and regulation of the intestinal microbiota–gut–lung homeostasis. [Display omitted] [ABSTRACT FROM AUTHOR]

Lung segmentation is often performed as a preprocessing step on chest Computed Tomography (CT) images because it is important for identifying lung diseases in clinical evaluation. Hence, research on lung segmentation has received much attention. Most of the conventional methods need the post-processing just like rolling ball method or morphology method to deal with the juxtapleural lung nodules or other lesions. To find a most robust method of lung segmentation, we propose a new algorithm based on an improved graph cuts algorithm with Gaussian mixture models (GMMs) in this paper. The core method models the foreground object and background of the CT images as a GMMs, and the weight or probability that each pixel belongs to the foreground object is calculated with expectation maximization (EM) algorithm. The corresponding graph is then created using these weights on the nodes and edges. And the segmentation is completed with the minimum cut theory. Experimental results show that the proposed method is very accurate and efficient, and can directly provide explicit lung regions without any postprocessing operations even in complex scenarios. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Jinxin oral liquid (JOL) is a traditional Chinese medicine (TCM) formula modified from ma-xing-shi-gan-tang, an ancient formula widely used in the treatment of respiratory diseases such as bronchitis, pneumonia, and asthma. In our previous studies, JOL was shown to safely and effectively treat viral pneumonia, especially that involving respiratory syncytial virus (RSV). Aim of the study To investigate the mechanism of the effect of JOL in RSV infected mice, using a metabolomics approach based on ultra-performance liquid chromatography coupled with linear ion trap quadrupole-Orbitrap mass spectrometry (UPLC/LTQ-Orbitrap–MS). Materials and methods BALB/c mice were divided into four groups, the control group (saline inoculation/no treatment), RSV group (RSV inoculation/saline treatment), RSV+JOL group (RSV inoculation/JOL treatment), and RSV+Riba group (RSV inoculation/ribavirin treatment). Plasma and lung tissue samples were collected 7 days after the inoculation/treatment protocols, and UPLC/LTQ-Orbitrap-MS method based on metabolomics was developed. Principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were utilized to identify biomarkers potentially associated with the anti-RSV activity of JOL. Results JOL was associated with reduced inflammatory responses in RSV-infected lung tissue. The combination of PCA and OPLS-DA revealed deviations in 11 biomarkers in plasma, and 16 biomarkers in lung tissue induced by RSV that were corrected with JOL treatment. These biomarkers were primarily components of metabolic pathways involving glycerophosphocholines, sphingolipids, and glycerolipids. JOL was able to restore the abnormal levels of these biomarkers detected in the plasma and lung tissue of RSV-infected mice to approximately normal levels. Conclusions This study suggested that JOL can treat RSV pneumonia effectively, partially by ameliorating the associated disturbances to lipid metabolism. The results provided insight into the anti-RSV mechanism of JOL, and also demonstrated that metabolomics is a valuable tool for investigating the efficacy of TCM treatment for RSV pneumonia, and the associated biomarkers involved. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Ipomoea asarifolia (Convolvulacae), commonly known as “morning glory” is found across West Africa. Preparations of the plant are used traditionally for the treatment of diverse ailments including diabetes, neuralgia, arthritic pain and stomach ache. This study was designed to assess the safety profile of the hydroethanolic leaf extract of I. asarifolia through a 90-day subchronic toxicity study in rats. Materials and methods I. asarifolia was administered p.o. at doses of 40, 200 and 1000 mg/kg to separate groups of rats for 90 days. Distilled water was given p.o. to rats in the control group. Some set of rats in each group were left for additional 30 days without administration of the extract for reversibility study. Animals were weighed weekly and relevant parameters were assayed at the end of the main and reversibility study periods. Results There was no significant change ( p >0.05) in the body weight of rats, and food and water intake in I. asarifolia treated groups compared with control. I. asarifolia (40–1000 mg/kg) significantly but reversibly reduced ( p <0.05, 0.001) sperm motility and count. The extract did not generally cause significant change ( p >0.05) in the weight of vital organs and haematological parameters except in the case of reversible reduction in the level of haemoglobin and red blood cell count ( p <0.01; 40 mg/kg). The level of biochemical parameters and electrolytes were not significantly changed ( p >0.05) except for the reversible reduction in the level of aspartate aminotransferase (AST; p <0.0001; 200 and 1000 mg/kg) and increase in the level of Na + ( p <0.01; 200 mg/kg). The level of kidney reduced glutathione (GSH) was reversibly increased ( p <0.01; 1000 mg/kg) while the level of enzymatic and non-enzymatic in vivo antioxidants was generally comparable and not significantly different ( p >0.05) from control in respect of all other vital organs. Histological presentations were generally normal in respect of the liver, kidneys, brain, heart, lungs, pancreas, spleen and testes. Conclusions The findings in this study suggest that the hydroethanolic leaf extract of I. asarifolia is relatively safe administered orally for an extended period with potential renal in vivo antioxidant activities. However, the extract may cause reversible male sterility, anaemia and hypernatraemia. [ABSTRACT FROM AUTHOR]

Aim of the study In Oriental countries, the dried fruits of Schisandra chinensis are extensively used in traditional medicine to treat asthma, gonorrhea, and other diseases. Recently, α-cubebenoate was isolated as an anti-inflammatory component from Schisandra chinensis . In the present study, the authors examined the anti-allergic effect of α-cubebenoate using in vivo and in vitro experiments. Materials and methods α-Cubebenoate was isolated from an extract of Schisandra chinensis fruits. Antigen-induced degranulation and Ca 2+ mobilization were measured in RBL-2H3 mast cells. In addition, BALB/c mice were sensitized with ovalbumin and aluminum hydroxide, and then challenged with ovalbumin for three consecutive days. α-Cubebenoate (1 mg/kg) was administered intraperitoneally 30 min before each ovalbumin challenge. Results In RBL-2H3 mast cells, α-cubebenoate inhibited antigen-induced degranulation and increase of intracellular Ca 2+ concentrations. In the ovalbumin-induced asthma model, α-cubebenoate suppressed bronchiolar structural changes induced by ovalbumin challenge. Furthermore, α-cubebenoate strongly inhibited accumulations of eosinophils, macrophages, and lymphocytes in bronchoalveolar lavage fluid. α-Cubebenoate also suppressed Th2 cytokines (IL-4 and IL-13) and TGF-β1 in lung tissues and in immune cells at the mRNA and protein levels. Conclusion α-Cubebenoate has an inhibitory effect on allergic inflammation and could be utilized as an agent for the treatment of asthma. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Houttuynia cordata (HC) has been used as a folk therapy to treat pulmonary infections. This study aimed to determine the role and mechanism of action of polysaccharides isolated from HC (HCP) in lipopolysaccharide (LPS)-induced ALI in the mice. Materials and methods LPS was delivered by the intratracheal route to Balb/c mice 2 h before HCP (40, 80 and 160 mg/kg) administration. Results The number of total cells, protein and tumor necrosis factor-α (TNF-α) concentrations in bronchoalveolar lavage fluid, the wet/dry weight ratio (w/d) of lungs and pulmonary pathology of each mouse were analyzed, it was found that HCP significantly alleviated ALI induced by LPS. Moreover, in lungs of mice, it was found that the infiltration of inflammatory cells, the expression of Toll-like receptor 4 and complement deposition were significantly decreased by HCP treatment. In vitro assays showed that C5a, a complement activation product, induced significant macrophage migration and treatment with HCP prevented it. The in vitro results also proved that LPS increased nitric oxide and pro-inflammatory cytokines (TNF-α, interleukin-6, and interleukin-1β) production, and HCP antagonized these effects of LPS. It was also found that HCP alone augmented secretion of some pro-inflammatory cytokines. Conclusion These results indicate that HCP may alleviate LPS induced lung inflammatory injury, which may be associated with its inhibitory effect on the over activation of complement and macrophages. This suggests a potential role to treat ALI. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Spilanthes africana is a plant used in several countries for the treatment of toothache, malaria, fracture, pneumonia, and dysentery. In order to establish the safety of aerial part of the plant extract, the acute and sub-acute toxicity of the aqueous extract of this plant has been evaluated in male and female young rats. Material and methods In acute toxicity, the effects of a single oral dose (2000 mg/kg and 5000 mg/kg) of the lyophilised aqueous extract have been determined. General behaviour, adverse effects and mortality were determined for up to 14 days. In sub-acute treatment, the effects of the extract in daily single oral administration at the doses of 250, 500 and 1000 mg/kg during 28 days were evaluated. One group treated at the dose of 1000 mg/kg for 28 days was let without treatment during 14 days to assess the possible reversibility of the harmful effects of the extract. Body weight, food and water intakes, biochemical and haematological parameters were recorded. Histopathological examination of liver, kidney and lungs were assessed. Results In acute study, a single administration of the aqueous extract at the doses of 2000 mg/kg or 5000 mg/kg did not induce mortality. Thus, the LD 50 of the aqueous extract of S. africana has been estimated higher than 5000 mg/kg. Four hours after administration of the extract, a reduction of the mobility, sensitivity to the noise and to touch has been observed. In sub-acute study, the administration of the extract during 28 days at all doses did not significantly modify the body weight. On the haematological analysis, a decrease of the rate of monocytes and a rise of lymphocytes counts were observed among the male group. In both sexes, it appeared a decrease of the rate of granulocytes two weeks after stopping the treatment. It has also been observed in different groups among the females, an increase of the mean corpuscular content and the mean concentration in haemoglobin as well as an increase of platelets. A significant decrease of transaminases, alkaline phosphatase, triglycerides, and a significant increase of total bilirubin compared to the normal group has been observed. There was a significant decrease in renal catalase in both sexes compared with different control groups. Besides, a significant increase of the kidney rates of glutathione and malondialdehyde have also been observed in the female treated at the doses of 1000 mg/kg. Histopathological analysis has shown vascular congestion and leucocyte infiltrations in the liver of animals treated at the dose of 1000 mg/kg. This congestion has been marked in satellite group. In the kidney female satellite group, tubular clarifications have been observed and disappear when stopping the treatment. Conclusion These results show that the aqueous extract of S. africana given by the oral route is slightly toxic. However in sub-acute treatment, higher doses could provoke functional and structural changes in the organism which could in part reversible. Thus the extract should be used with caution. [ABSTRACT FROM AUTHOR]

Aim of the study Asthma is an ailment of airways characterized by activation of the T helper (Th) 2 lymphocytes and subsequent movement of inflammatory cells. Boerhavia procumbens of family Nyctaginaceae is locally used for the treatment of asthma, cough, hemorrhoids, dropsy, cardiac, eyes and kidney problems. We have evaluated its methanol extract (BPM) as a therapeutic candidate for asthma against toluene diisocyanate (TDI) allergic model in rat. The BPM extract was obtained from the whole plant of B. procumbens in methanol. Sprague-Dawley male 36 rats (200–250 g) were categorized into 6 groups having six rats in each category. The animals were provoked (10%) and sensitized (5%) by TDI. Animals of groups I–III were vehicle control (ethyl acetate), diseased control (TDI) and reference control (TDI+dexamethasone {2.5 mg/kg bw}), respectively. Animals of group IV (TDI+200 mg/kg bw) and group V (TDI+400 mg/kg bw) were administered with BPM whereas group VI was administered with 400 mg/kg bw alone of BPM. Protective effects of BPM were determined by counting the number of leucocytes and estimation of interleukines in blood, bronchoalveolar lavage (BAL) and in in vitro culture of spleen cells. Estimation of antioxidant enzymes, lipid peroxides and H 2 O 2 and histopathology of lungs were carried out for antioxidant potential of plant extract used. Results Methanol extract of B. procumbens suppressed the asthmatic symptoms and inhibited the infiltration of eosinophils and lymphocytes in lungs of TDI provoked rats. Administration of BPM to TDI provoked rats, dose dependently, inhibited the release of interleukins (IL)-2 in serum and IL-4, IL-6 interferon gamma (IFN-γ) in bronchoalveolar lavage (BAL) and in in vitro culture of spleen cells, and ameliorated the oxidative stress in lung tissues. Quantitative scoring of the lung histopathology exhibited protective effects of BPM and the inflammation, mucus, thickening of peribronchial smooth muscle layer and subepithelial deposition of collagen induced with TDI were ameliorated. The BPM has the anti-inflammatory properties that may be used to treat the asthma and inflammatory related ailments. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Pseudolysimachion rotundum var . subintegrum (Speedwell, Plantaginaceae) is used as a traditional herbal medicine for treating bronchitis, cough and asthma in Korea, China, Russia, and Europe. Aim of the study In this study, we investigated the protective effects of the novel iridoid glycoside, piscroside C (compound 1) isolated from the methanolic extract of P. rotundum var. subintegrum against inflammatory responses using a cigarette smoke induced chronic obstructive pulmonary disease (COPD) and TNF-α-stimulated human airway epithelial NCI-H292 cells. Materials and methods The novel iridoid glycoside piscroside C was isolated from the methanolic extract of P. rotundum var. subintegrum . The chemical structure was established by NMR, HRESIMS, and optical rotation. In in vivo experiment, the mice received 1 h of cigarette smoke for 3 days. Piscroside C was administered to mice by oral gavage 1 h before cigarette smoke exposure for 3 days. In in vitro experiment, we evaluated the effect of piscroside C on proinflammatory mediators in H292 cells stimulated with TNF-α. Results Piscroside C significantly reduced the neutrophil influx, reactive oxygen species production, IL-6, TNF-α, and elastase activity in bronchoalveolar lavage fluid in COPD animals. In addition, piscroside C attenuated NF-κB and IκB phosphorylation, leading to reduced recruitment of inflammatory cells into the lung tissue. Consistent with the results of in vivo experiment, piscroside C significantly inhibited the expression of inflammatory cytokines (IL-6, IL-8 and IL-1β) by inhibiting NF-κB activation, as resulting decrease in the phosphorylation of IKKβ, IκBα and TAK1 in TNF-α-stimulated H292 cells. Conclusion These findings indicate that piscroside C effectively inhibits inflammatory responses, which is an important process in the development of COPD through suppression of IKK/NF-κB activation. Our study suggest that piscroside C might represent a useful therapeutic for the treatment of inflammatory airway disease. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Eupafolin, a major bioactive compound found in Phyla nodiflora, has the anti-inflammatory property. Upregulation of cell adhesion molecules in the lung airway epithelium is associated with the epithelium–leukocyte interaction and plays a critical role in the pathogenesis of lung airway inflammatory disorders. To investigate the effects of eupafolin on tumor necrosis factor-α (TNF-α)-induced intercellular cell adhesion molecule-1 (ICAM-1) expression in A549 human lung airway epithelial cells and the underlying mechanisms. Materials and methods The effect of eupafolin on ICAM-1 expression in A549 cells were examined by Western blotting and immunofluorescent staining. The mice were injected intraperitoneally with or without eupafolin and then were left untreated or were injected intratracheally with TNF-α. To detect the effect of eupafolin on ICAM-1 expression, the lung tissues were also examined by Western blotting and immunohistochemical staining. Results Eupafolin pretreatment reduced the TNF-α-induced ICAM-1 expression and also the ERK1/2, JNK, p38, and AKT/PI3K phosphorylation. However, the increase in ICAM-1 expression with TNF-α treatment was unaffected by p38 and PI3K inhibitors. Eupafolin decreased the TNF-α-induced NF-κB p65 activation and its nuclear translocation. Furthermore, eupafolin reduced ICAM-1 expression in the lung tissues of TNF-α-treated mice. Conclusions Eupafolin exerts its anti-inflammatory activity by suppressing the TNF-α-induced ICAM-1 expression and subsequent monocyte adhesion via AKT/ERK1/2/JNK phosphorylation and nuclear translocation of NF-κB p65. These results suggest that eupafolin may represent a novel therapeutic agent targeting epithelial activation in lung inflammation. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Impatiens textori Miq. ( I. textori, Balsaminaceae) is a traditional medicinal herb used for centuries to treat several inflammatory related skin infections and allergic disorders in Asian countries. Aim of the study In this study, we elucidated the effects of whole plant extracts of I. textori on inflammasome activation using in vitro and in vivo models. Materials and methods LPS-stimulated murine bone marrow macrophages were used to study the regulatory effect of I. textori extract (IT) on inflammasome activation. ATP, nigericin and MSU were used as danger-associated molecules to activate the NLRP3 inflammasome. An LPS-induced acute lung injury (ALI) mouse model was used to study the in vivo effect of IT on inflammasome activation. Results IT treated at 25, 50, and 100 μg/mL concentrations suppressed interleukin-1β secretion through the attenuation of NLRP3 inflammasome activation ( p <0.001 at 100 μg/mL) leading to the decreased amount of ASC oligomerization and caspase-1 maturation. For the in vivo model, IT inhibited the NLRP3 expression and cell recruitment at the lung tissue in the ALI mouse model. Conclusion IT exhibited potent anti-inflammatory effects via the attenuation of NLRP3 inflammasome activation supporting the traditional claims and may provide a valuable therapeutic strategy in treating various inflammation-related disorders. [ABSTRACT FROM AUTHOR]