Potential efficacious materials investigation of Yi-Yi Mixture based on Metabolome-oriented network pharmacology strategy.

Yi-Yi Mixture, an efficient Chinese medicine preparation composed of four herbal medicines, has been used in clinical practice in China for the treatment of acute pancreatitis over twenty years. However, its functional materials against acute pancreatitis remains unclear, which is a huge obstacle for quality control. In this study, a metabolome-oriented network pharmacology strategy was proposed to clarify its potential substances and further screen out quality markers. Firstly, an Ultra-High performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry method was utilized to profile the chemical constituents in Yi-Yi Mixture. Secondly, metabolic exposure of chemical constituents as well as their global metabolites produced in biological systems were profiled and defined as metabolome of Yi-Yi Mixture. Then, the metabolome targets were predicted based on network analysis. As a result, a total of 66 chemical components were characterized, including 6 stilbenes, 21 anthraquinones, 7 phenols, 13 neolignans, 3 naphthalenes and 16 other types. Moreover, metabolic profiles of YYM (32 prototypes and 37 metabolites) were analyzed in rat bio-samples. Among them, resveratrol, emodin, chrysophanol, rhein and their derivatives were detected in multiple tissues/organs, revealing their potential as key pharmacodynamic substances. These were further confirmed by metabolome-oriented network analysis and molecular docking techniques. This is the first comprehensive investigation on chemical and metabolic profiles of Yi-Yi Mixture, and the results provided scientific foundation for further research on quality control and clinical-safe medication administration.

Attenuating effect of Ginsenoside Rb1 on LPS-induced lung injury in rats.

BACKGROUND: Sepsis causes neutrophil sequestration in the lung which leads to acute lung injury (ALI). Radix Ginseng (RG), a traditional herb used as herbal remedy in eastern Asia for thousands of years, which has been traditionally used in China to improve blood circulation and ameliorate pathological hemostasis. This study investigated whether Ginsenoside Rb1, the main components of RG, can attenuate ALI induced by LPS. METHODS: In vivo, 30 male Wistar rats were divided into three groups (n = 10 each groups) on the basis of the reagent used, which were subjected to LPS injection with or without Ginsenoside Rb1 (5 mg/kg) treatments to induce ALI model. Lung injury was assessed by pulmonary histology, lung wet-weight to dry-weight (W/D) ratio, the number of myeloperoxidase (MPO) positive cells, immunohistochemical analysis of intercellular adhesion molecule-1 (ICAM-1), gene expression of ICAM-1, ultrastructure changes of pulmonary microvasculature, concentration of inflammatory markers and in plasma. In vitro, pulmonary microvascular endothelial cells (PMVECs) were stimulated with LPS in the presence and absence of Ginsenoside Rb1 (50 mM), nuclear factor-κB (NF-κB) p65 was measured by immunocytochemistry staining and western blotting. RESULTS: Infusion of LPS induced lung injury, in vivo, as demonstrated by pulmonary edema with infiltration of neutrophils and hemorrhage, the increase in lung W/D ratio, the number of MPO positive cells, the level of inflammatory markers such as TNF-α, MCP-1 and IL-8, enhanced expression of ICAM-1 and ICAM-1 gene. Moreover, resulted in the changes of intercellular junctions in the endothelial cells of pulmonary microvasculature. In vitro, the significant increased release of NF-κB p65 and its subsequent translocation into the nucleus in PMVECs were observed. In contrast, Ginsenoside Rb1 treatment significantly ameliorated the LPS-induced lung injury, as judged by the marked improvement in all these indices. CONCLUSIONS: These results indicate that Ginsenoside Rb1 attenuated LPS-induced lung injury through an inhibition of the inflammatory signaling pathway, besides the direct inhibitory effect on proinflammatory molecules.

Improving effect of Sivelestat on lipopolysaccharide-induced lung injury in rats.

Sepsis causes neutrophil sequestration in the lung, which leads to acute lung injury (ALI). Neutrophil elastase (NE) is thought to play an important role in the pathogenesis of ALI. This study investigated whether Sivelestat, a specific NE inhibitor, can attenuate ALI induced by lipopolysaccharide (LPS). In vivo, 30 male Wistar rats were divided into three groups (n = 10 each groups) on the basis of the reagent used, which were subjected to LPS injection with or without Sivelestat treatments to induce ALI model. Lung injury was assessed by pulmonary histology, lung wet-weight to dry-weight (W/D) ratio, immunohistochemical analysis of intercellular adhesion molecule-1 (ICAM-1), the number of myeloperoxidase (MPO)-positive cells, and gene expression of ICAM-1. In vitro, pulmonary microvascular endothelial cells (PMVECs) were stimulated with LPS in the presence and absence of Sivelestat; nuclear factor-κB (NF-κB) p65 was measured by immunocytochemistry staining and Western blotting. Infusion of LPS induced lung injury, in vivo, as demonstrated by pulmonary edema with infiltration of neutrophils, the increase in lung W/D ratio, the number of MPO-positive cells and enhanced expression of ICAM-1 and ICAM-1 gene. In vitro, the significant increased release of NF-κB p65 and its subsequent translocation into the nucleus in PMVECs. In contrast, Sivelestat treatment significantly ameliorated the LPS-induced lung injury, as judged by the marked improvement in all these indices. These results indicated that inhibition of NE attenuated LPS-induced lung injury through an inhibition of the inflammatory signaling pathway, besides the direct inhibitory effect on NE.

Immediate and long-term results of bronchial artery embolization for hemoptysis due to benign versus malignant pulmonary diseases.

BACKGROUND: Bronchial artery embolization (BAE) is widely used for the treatment of hemoptysis. The immediate and long-term results of BAE for hemoptysis in patients with benign and malignant pulmonary diseases were inconsistent in previous studies and were thus investigated. METHODS: This was a retrospective review of the clinical records of 154 patients (108 with benign disease and 46 with malignant disease) who received BAE for hemoptysis from January 2005 to June 2011 at the Chinese People's Liberation Army General Hospital. RESULTS: Immediate cessation of hemoptysis was achieved in 98 patients with benign disease (90.7%) and 42 patients with malignancy (91.3%). The long-term control rate of hemoptysis in patients with benign disease was 74.3% (80/108) at 1 year, significantly higher than in patients with cancer (16/46, 35.5%, P < 0.01). The worst outcomes in the benign and malignant groups were observed in patients with aspergilloma and squamous cell lung cancer, respectively. The average number of abnormal vessels on bronchial arteriography was higher in the benign group than in the malignant group (3 ± 1.3 versus 2 ± 1.1, respectively, P < 0.01). Moreover, recurrent hemoptysis was independently associated with the presence of massive hemoptysis and bronchial-pulmonary artery shunt in both groups (P < 0.05). CONCLUSIONS: BAE is a relatively safe procedure for patients with hemoptysis. Immediate control of hemoptysis with BAE is achieved in most cases, but the long-term hemoptysis control rate is worse in malignant lung diseases than in benign conditions, especially among patients with squamous cell lung cancer.

microRNAs as tumor inhibitors, oncogenes, biomarkers for drug efficacy and outcome predictors in lung cancer (review).

Lung cancer remains the leading cause of cancer-related death worldwide for both men and women, and non-small cell lung cancer (NSCLC) accounts for approximately 80% of all cases. Despite improvements in early diagnosis and newly developed therapies, the 5-year survival rate for NSCLC patients remains low (15%). Therapy in NSCLC has reached a plateau. Understanding genomic medicine may provide insight into the oncogenesis of lung cancer and open the door to molecular diagnosis, new biomarkers and a more accurate prognosis of lung cancer. It is well known that almost half of the genes regulated by microRNAs (miRNAs) are located in cancer-associated genomic regions. In the present study, we discuss the potential of miRNAs to function as suppressors and biomarkers for chemoresistance and prognosis of lung cancer.

[The relationship between inflammatory mediators and pulmonary hypertension in patients with chronic obstructive pulmonary disease].

OBJECTIVE: The levels of C-reactive protein (CRP), tumor necrosis factor (TNF)-α, brain natriuretic peptide (BNP) and endothelin-1 (ET-1) were investigated to analyze the systemic inflammation in chronic obstructive pulmonary disease (COPD) patients with and without pulmonary hypertension. METHODS: From January 2006 to December 2010, 89 patients with COPD were enrolled in our hospital. There were 67 males and 22 females, with a mean age of (70 ± 7) and a mean FEV(1) of (47 ± 13)%. Pulmonary pressure was assessed by Doppler echocardiography. The levels of plasma BNP, TNF-α and ET-1 were measured by enzyme-linked immunosorbent assay kits. High-sensitivity plasma CRP level was assessed by chemiluminescent immunoassay. RESULTS: Forty-two patients were classified as COPD with pulmonary hypertension group and 47 patients as COPD without pulmonary hypertension group. The level of CRP [51.4 mg/L (20.1 - 92.0) mg/L], ET-1 [5.9 ng/L (3.7 - 10.4) ng/L] and BNP [303.2 ng/L (112.5 - 824.7) ng/L] in patients with pulmonary hypertension were significantly higher than in that in patients without hypertension, CRP [26.7 mg/L (11.5 - 62.9) mg/L], ET-1 [2.1 ng/L (1.3 - 4.7) ng/L] and BNP [143.7 ng/L (85.5 - 306.7) ng/L]. The level of TNF-α showed no difference between the 2 groups [8.5 ng/L (4.8 - 13.7) ng/L and 6.7 ng/L (3.2 - 10.3) ng/L], respectively. Multivariate analysis showed that PaO2 (P < 0.05), CRP (P < 0.05) and BNP (P < 0.05) could predict pulmonary hypertension independently. CONCLUSION: The level of CRP, ET-1 and BNP were related to pulmonary hypertension in COPD patients, suggesting that systemic inflammation play a role in the pathogenesis of pulmonary hypertension in COPD.

[The relationship between sputum eosinophils and responses to treatment of inhaled glucocorticoids in patients with persistent asthma].

OBJECTIVE: To evaluate the treatment responses of asthmatics with and without sputum eosinophilia to inhaled glucocorticoids, and therefore to verify whether low sputum eosinophils predict poor response to treatment with inhaled glucocorticoids. METHODS: Forty-two symptomatic asthmatic patients, who had not received glucocorticoid therapy in the 3 months preceding the study, were examined before and 1 month and 3 months after treatment with inhaled glucocorticoids. At each visit, all patients underwent spirometry, symptom scoring and sputum induction. The level of eosinophil cationic protein (ECP) in the sputum supernatants was measured by radioimmunoassay. The patients were divided into 2 groups according to sputum eosinophil (EOS) percentages, an EOS group (EOS > 3%) and a non-EOS group (EOS < 3%). The response to inhaled glucocorticoid therapy (as measured by symptom scores and FEV(1)% pred) and the changes of sputum measurements were compared between the 2 groups. RESULTS: In the EOS group, the baseline EOS [0.080 (0.063 - 0.178)] and ECP level [(324 +/- 149) microg/L] were significantly higher than those of the non-EOS group [0.017 (0.006 - 0.021) and (152 +/- 68) microg/L, respectively, t = 4.40, 3.33, both, all P < 0.01]. Baseline FEV(1), FEV(1)% pred and symptom scores were not different between the 2 groups [EOS group: (1.98 +/- 0.67) L, (65 +/- 20)%, 7.0 (5.0 - 10.0), non-EOS group: (2.07 +/- 1.05) L, (66 +/- 27)%, 5.0 (2.0 - 9.0), t = -0.62, -0.09, 1.32, respectively, all P > 0.05]. After 1 month and 3 months inhaled glucocorticoid therapy, the sputum EOS, ECP, the symptom score, FEV(1) and FEV(1)% pred were [0.019 (0.010 - 0.060), [0.036 (0.006 - 0.070); (173 +/- 153) microg/L, (173 +/- 122) microg/L; 3.0 (1.0 - 6.0), 3.0 (1.0 - 5.0); (2.42 +/- 0.64) L, (2.43 +/- 0.76) L; (77 +/- 13)%, (77 +/- 18)%; respectively in the EOS group, which were significantly different as compared to baseline values (F = 6.73, 6.71, 5.93, 7.38, 5.78, respectively, all P < 0.05). But in the non-EOS group, the sputum EOS, ECP, the symptom score, FEV(1) and FEV(1)% pred were 0.013 (0.000 - 0.025), 0.012 (0.004 - 0.031), (111 +/- 50) microg/L, (117 +/- 50) microg/L; 3.0 (0.0 - 6.0), 3.0 (1.0 - 7.3), (2.22 +/- 0.86) L, (2.21 +/- 0.24) L, (71 +/- 20)%, (65 +/- 21)%; respectively at 1 and 3 months, which showed that the sputum EOS, FEV(1) and FEV(1)% pred did not change (F = 1.98, 0.80, 1.37, respectively, all P > 0.05), but the ECP level and the symptom score improved (F = 3.78, 3.59, respectively, both P < 0.05). Multiple stepwise regression showed that baseline FEV(1), severity degree and sputum EOS correlated significantly with changes in FEV(1) after treatment. Among the baseline indexes examined, sputum EOS had the highest negative predictive value (89.5%) for the response to treatment. CONCLUSIONS: In asthmatics with low sputum EOS, inhaled glucocorticoid therapy for 3 months failed to improve pulmonary function. The result confirmed that low sputum EOS was the best predictor for poor glucocorticoid effect in asthma.