OBJECTIVES: To investigate the role and mechanism of fibroblast growth factor (FGF) 19 in inflammation-induced injury of vascular endothelial cells caused by high glucose (HG). METHODS: Human umbilical vein endothelial cells (HUVECs) were randomly divided into four groups: control, HG, FGF19, and HG+FGF19 (n=3 each). The effect of different concentrations of glucose and/or FGF19 on HUVEC viability was assessed using the CCK8 assay. Flow cytometry was utilized to examine the impact of FGF19 on HUVEC apoptosis. Levels of interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), total superoxide dismutase (T-SOD), and malondialdehyde (MDA) were measured by ELISA. Real-time quantitative PCR and Western blotting were used to determine the mRNA and protein expression levels of vascular endothelial growth factor (VEGF), nuclear factor erythroid 2 related factor 2 (Nrf2), and heme oxygenase-1 (HO-1). Cells were further divided into control, siRNA-Nrf2 (siNrf2), HG, HG+FGF19, HG+FGF19+negative control, and HG+FGF19+siNrf2 groups (n=3 each) to observe the effect of FGF19 on oxidative stress injury in HUVECs induced by high glucose after silencing the Nrf2 gene. RESULTS: Compared to the control group, the HG group exhibited increased apoptosis rate, increased IL-6, iNOS and MDA levels, and increased VEGF mRNA and protein expression, along with decreased T-SOD activity and decreased mRNA and protein expression of Nrf2 and HO-1 (P<0.05). Compared to the HG group, the HG+FGF19 group showed reduced apoptosis rate, decreased IL-6, iNOS and MDA levels, and decreased VEGF mRNA and protein expression, with increased T-SOD activity and increased Nrf2 and HO-1 mRNA and protein expression (P<0.05). Compared to the HG+FGF19+negative control group, the HG+FGF19+siNrf2 group had decreased T-SOD activity and increased MDA levels (P<0.05). CONCLUSIONS FGF19 can alleviate inflammation-induced injury in vascular endothelial cells caused by HG, potentially through the Nrf2/HO-1 signaling pathway.
Humans ; NF-E2-Related Factor 2/genetics* ; Signal Transduction ; Human Umbilical Vein Endothelial Cells/drug effects* ; Fibroblast Growth Factors/pharmacology* ; Heme Oxygenase-1/physiology* ; Apoptosis/drug effects* ; Glucose ; Inflammation ; Interleukin-6/analysis* ; Vascular Endothelial Growth Factor A/genetics* ; Nitric Oxide Synthase Type II/analysis* ; Cells, Cultured

The stem and branch extract of Tripterygium wilfordii (Celastraceae) afforded seven new dihydroagarofuran sesquiterpene polyesters [tripterysines A-G (1-7)] and eight known ones (8-15). The chemical structures of these new compounds were established based on combinational analysis of HR-ESI-MS and NMR techniques. The absolute configurations of tripterysines A-C (1-3) and E-G (5-7) were determined by X-ray crystallographic analysis and circular dichroism spectra. All the compounds were screened for their inhibitory effect on inflammation through determining their inhibitory effect on nitric oxide production in LPS-induced RAW 264.7 cells and the secretion of inflammatory cytokines TNF-α and IL-6 in LPS-induced BV2 macrophages. Compound 9 exhibited significant inhibitory activity on NO production with an IC₅₀ value of 8.77 μmol·L^-1. Moreover, compound 7 showed the strongest inhibitory effect with the secretion of IL-6 at 27.36%.
Tripterygium/chemistry* ; Esters/pharmacology* ; Interleukin-6 ; Lipopolysaccharides/pharmacology* ; Plant Leaves/chemistry* ; Anti-Inflammatory Agents/chemistry* ; Nitric Oxide/analysis* ; Sesquiterpenes/chemistry* ; Molecular Structure

Objective: To investigate the changes of intestinal wall barrier function and its correlation with infection occurrence in patients with cirrhotic portal hypertension. Methods: 263 patients with cirrhotic portal hypertension were split into: the clinically evident portal hypertension (CEPH) combined with infection group (n = 74); CEPH group (n = 104); and Non-CEPH group (n = 85). Among them, 20 CEPH patients and 12 non-CEPH patients in non-infection status were subjected to sigmoidoscopy. Immunohistochemical staining was used to detect the expression of trigger receptor-1 (TREM-1), CD68, CD14, the inducible nitric oxide synthase molecule, and Escherichia coli (E.coli) in the medullary cells of the colon mucosa. An enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of soluble myeloid cell trigger receptor-1 (sTREM-1), soluble leukocyte differentiation antigen-14 subtype (sCD14-ST) and intestinal wall permeability index enteric fatty acid binding protein (I-FABP). Fisher's exact probability method, one-way ANOVA, Kruskal-Wallis-H test, Bonferroni method, and Spearman correlation analysis were used for statistical analysis. Results: The serum sTREM-1 and I-FABP levels were higher in CEPH patients than those of non-CEPH patients in the non-infectious state (P < 0.05), but the difference in blood sCD14-ST levels was not statistically significant (P > 0.05). Serum levels of sTREM-1, sCD14-ST, and I-FABP in infected patients were higher than those in patients without a concurrent infection (P < 0.05). Serum sCD14-ST levels were positively correlated with serum sTREM-1, C-reactive protein (CRP), and procalcitonin (PCT), and sTREM-1 levels were also positively correlated with CRP and PCT (r > 0.5, P < 0.001). The rates of CD68, inducible nitric oxide synthase, CD14-positive cells, and E.coli-positive glands were higher in the intestinal mucosa of the CEPH group than those of the control group (P < 0.05). Spearman's correlation analysis showed that the rate of E.coli-positive glands in CEPH patients was positively correlated with the expression of molecular markers CD68 and CD14 in the lamina propria macrophages. Conclusion: Patients with cirrhotic portal hypertension have increased intestinal permeability and inflammatory cells, accompanied by bacterial translocation. Serum sCD14-ST and sTREM-1 can be used as indicators to predict and evaluate the occurrence of infection in patients with cirrhotic portal hypertension.
Humans ; Nitric Oxide Synthase Type II ; Lipopolysaccharide Receptors ; Prospective Studies ; Biomarkers ; C-Reactive Protein/analysis* ; Liver Cirrhosis/complications* ; Hypertension, Portal

OBJECTIVES: To study the association of fractional exhaled nitric oxide (FeNO) and nasal nitric oxide (nNO) with asthma control and their value in the diagnosis of allergic rhinitis in children. METHODS: A total of 186 children aged 5-12 years, who attended the outpatient service of the Department of Respiration, Shanghai Children's Hospital due to bronchial asthma and/or allergic rhinitis or who underwent physical examination, were enrolled as subjects, with 52 children in the asthma group, 60 children in the asthma+allergic rhinitis group, 36 children in the allergic rhinitis group, and 38 children in the control group. FeNO, nNO, and pulmonary function were compared between groups. RESULTS: The asthma+allergic rhinitis, asthma, and allergic rhinitis groups had a significantly higher level of FeNO than the control group (P<0.05). The asthma+allergic rhinitis and allergic rhinitis groups had a significantly higher level of nNO than the asthma and control groups (P<0.05). The uncontrolled asthma and partially controlled asthma groups had significantly higher levels of FeNO and nNO than the completely controlled asthma group (P<0.05). The receiver operating characteristic (ROC) curve analysis showed that nNO had an area under the ROC curve of 0.91, with a sensitivity of 80.0% and a specificity of 89.5% in the diagnosis of allergic rhinitis in children with asthma (P<0.05). CONCLUSIONS The combined measurement of nNO and FeNO can be used to evaluate the control of asthma, and the measurement of nNO can help with the diagnosis of allergic rhinitis in children with bronchial asthma.
Asthma/diagnosis* ; Breath Tests ; Child ; Child, Preschool ; China ; Fractional Exhaled Nitric Oxide Testing ; Humans ; Nitric Oxide/analysis* ; Rhinitis, Allergic/diagnosis*

Objective: To explore the association between size-fractionated particle number concentrations (PNC) and respiratory health in children. Methods: From November 2018 to June 2019, there were 65 children aged 6-9 years from an elementary school in shanghai recruited in this panel study with three rounds of follow-up. The forced vital capacity (FVC), forced expiratory volume in the first second (FEV₁), and exhaled nitric oxide (FeNO) levels were measured and buccal mucosa samples of children were collected at each follow-up visit. The level of PNC, temperature and humidity of the elementary school was monitored from 3 days before each physical examination to the end of the physical examination. The linear mixed effects model was used to analyze the association between PNC and indicators of respiratory health in children. Results: Linear mixed effects model analysis revealed that, at lag 2 day, an interquartile range increase in PNC for particles measuring 0.25-0.40 μm was associated with the absolute changes in FVC, FEV₁ and abundance-based coverage estimator (ACE) about -60.15 ml (95%CI:-88.97 ml, -31.32 ml), -34.26 ml (95%CI:-63.22 ml, -5.31 ml), -6.00 (95%CI:-9.15, -2.84) and percentage change in FeNO about 12.10% (95%CI: 3.05%, 21.95%), respectively. These adverse health effects increased with the decrease of particle size. Conclusion: The short-term exposure to particulate matter is associated with reduced lung function, buccal microbe diversity and higher airway inflammation level among children. These adverse health effects may increase with the decrease of particle size.
Air Pollutants/analysis* ; Child ; China ; Environmental Exposure/analysis* ; Humans ; Lung ; Nitric Oxide ; Particulate Matter/adverse effects* ; Vital Capacity

OBJECTIVE: To investigate the impact of a history of atopy on the value of fractional exhaled nitric oxide (FENO) for predicting sputum eosinophils in patients with chronic cough. METHODS: A total of 868 patients with persistent cough lasting more than 3 weeks without pulmonary infection were enrolled, including 119 patients with subacute cough (defined as cough lasting 3-8 weeks) and 749 with chronic cough (longer than 8 weeks). The predictive value of FENO level for sputum eosinophilia was analyzed using receiver-operating characteristic (ROC) curve analysis, and the area under the curve (AUC) was calculated. The atopy status of the patients was determined by screening for history of allergy, hay fever, or animal or food allergies. RESULTS: Of the 868 patients enrolled, 173 patients (19.9%) had eosinophilic airway inflammation (EAI). In the overall patients, the median (Q1, Q3) FENO level was 18 (12, 35) ppb, ranging from 5 to 300 ppb. The patients with chronic cough and a positive history of atopy had a higher median FENO level than those without atopy (24 [13, 50] vs 18 [11, 34]; Z=2.25, P= 0.029), and FENO level was significantly correlated with EAI (r=0.281, P < 0.001). The AUCs of FENO for diagnosis of airway eosinophilia in patients with atopy and those without atopy were 0.677 (95% CI: 0.548-0.806) and 0.708 (95% CI: 0.660-0.756), respectively. The optimal cut-off value of FENO for diagnosing EAI was higher in patients with atopy than in those without atopy (72 vs 28.5 ppb). CONCLUSION A history of atopy reduces the predictive value of FENO level for EAI in patients with chronic cough, suggesting the importance of examining the atopic status when interpreting test results of FENO.
Humans ; Cough/diagnosis* ; Exhalation ; Fractional Exhaled Nitric Oxide Testing ; Nitric Oxide/analysis* ; Eosinophilia ; Chronic Disease ; Inflammation

Jatrogricaine A (1), a new diterpenoid possessing a 5/6/6/4 carbon ring system, together with eight known diterpenoids (2-9) were isolated from the stems of Jatropha podagrica. Their structures were elucidated by extensive spectroscopic methods and the absolute configuration of 1 was determined by single crystal X-ray diffraction analysis. All compounds were evaluated for their anti-inflammatory activities in vitro, and compound 3 showed significant inhibitory effects against nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW264.7 macrophage cells with an IC of 13.44 ± 0.28 μmol·L, being comparable to the positive control, quercetin (IC 17.00 ± 2.10 μmol·L).
Animals ; Anti-Inflammatory Agents ; chemistry ; pharmacology ; Carbon ; analysis ; Diterpenes ; chemistry ; pharmacology ; Inhibitory Concentration 50 ; Jatropha ; chemistry ; Lipopolysaccharides ; toxicity ; Macrophages ; drug effects ; metabolism ; Mice ; Molecular Structure ; Nitric Oxide ; metabolism ; Plant Extracts ; chemistry ; pharmacology ; Plant Stems ; chemistry ; RAW 264.7 Cells

BACKGROUND: The left internal thoracic artery (LITA) has been used as the first conduit of choice in coronary artery bypass grafting (CABG) because of excellent long-term patency and outcomes. However, no studies have examined substances other than nitric oxide that could be beneficial for the bypass conduit, native coronary artery or ischemic myocardium. This study was conducted to evaluate differences in metabolic profiles between the LITA and ascending aorta using gas chromatography-time of flight-mass spectrometry (GC-TOF-MS). METHODS: Twenty patients who underwent CABG using the LITA were prospectively enrolled. Plasma samples were collected simultaneously from the LITA and ascending aorta. GC-TOF-MS based untargeted metabolomic analyses were performed and a 2-step volcano plot analysis was used to identify distinguishable markers from two plasma metabolome profiles. Semi-quantitative and quantitative analyses were performed using GC-TOF-MS and enzyme-linked immunosorbent assay, respectively, after selecting target metabolites based on the metabolite set enrichment analysis. RESULTS: Initial volcano plot analysis demonstrated 5 possible markers among 851 peaks detected. The final analysis demonstrated that the L-cysteine peak was significantly higher in the LITA than in the ascending aorta (fold change = 1.86). The concentrations of intermediate metabolites such as L-cysteine, L-methionine and L-cystine in the ‘cysteine and methionine metabolism pathway' were significantly higher in the LITA than in the ascending aorta (2.0-, 1.4- and 1.2-fold, respectively). Quantitative analysis showed that the concentration of hydrogen sulfide (H2S) was significantly higher in the LITA. CONCLUSION: The plasma metabolome profiles of the LITA and ascending aorta were different, particularly higher plasma concentrations of L-cysteine and H2S in the LITA.
Aorta ; Chromatography, Gas ; Coronary Artery Bypass ; Coronary Vessels ; Cysteine ; Cystine ; Enzyme-Linked Immunosorbent Assay ; Humans ; Hydrogen Sulfide ; Mammary Arteries ; Mass Spectrometry ; Metabolism ; Metabolome ; Metabolomics ; Methionine ; Myocardium ; Nitric Oxide ; Plasma ; Prospective Studies ; Spectrum Analysis

This study aims to compare the internal chemical composition and appearance indifferent growth patterns and years of Saposhnikovia divaricata decoction pieces,which was applied to explore the effect of growth patterns and years on its quality. The appearance characteristic data of 55 batches of different growth patterns and years of S. divaricata were collected using PANTONE color card.High performance liquid chromatography( HPLC) was used to determine the contents of prim-O-glucosyl-cinmifugin,cimifugin,4-O-β-D-glucosyl-5-O-methylvisamminol and sec-O-glucosylhamaudol. The content of alcohol soluble extract and water-soluble extract were determined by hot-dip method. The content of volatile oil was determined by steam distillation. The correlation between growth patterns and years and the contents of 4 chromones,extracts and volatile oil were analyzed by modern statistical methods. Also,the method of comprehensively evaluating the quality of Chinese herbal pieces was developed by combining the growth patterns and years,appearance and chemical indexes. MTT assay was used to evaluate the effects on the survival rate of RAW264. 7 cells at four different concentrations of chromones and LPS was used to stimulate well-growing RAW264. 7 cells to establish an inflammatory model. The contents of NO and TNF-α in cell supernatant were detected by NO test kit and ELISA method. The contents of alcohol soluble extracts and water-soluble extracts in different growth patterns and years are: wild productsperennial cultivation>annual cultivation; the contents of four chromones are: wild products>perennial cultivation and annual cultivation. There was no significant difference between the sum of the two indexes in the Pharmacopoeia of perennial cultivation and wild products. 4 chromones showed no toxicity to RAW264. 7 cells at 5 mg·L-1. The release of NO and TNF-α was inhibited by 4 chromones and the anti-inflammatory effect of cimifugin was the best. In summary,there are obvious differences in appearance characteristics,internal quality and effects between different growth patterns and years. It showed that the wild products were superior to the perennial cultivation and the perennial cultivation was superior to the annual cultivation. In order to alleviate the shortage of wild S. divaricata resources,it is suggested that the Chinese Pharmacopoeia standard should increase the character of decoction pieces of perennial cultivation,and properly raise the limit requirement of the sum of the two indexes in the Chinese Pharmacopoeia to ensure the clinical demands and effect.
Animals ; Apiaceae/growth & development* ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/standards* ; Mice ; Nitric Oxide/metabolism* ; Oils, Volatile/analysis* ; RAW 264.7 Cells ; Tumor Necrosis Factor-alpha/metabolism*

OBJECTIVES: Simvastatin has been reported to attenuate the development of pulmonary hypertension through increased apoptosis as well as reduced proliferation of smooth muscle cells in obstructive vascular lesions. Microarray experiment can accomplish many genetic tests in parallel. The purpose of this study is to evaluate altered expressions of gene in rat hearts with monocrotaline (MCT)-induced pulmonary arterial hypertension after simvastatin treatment. METHODS: Six-week-old male rats were grouped as follows: control group (C group, saline injection), M group (MCT 60 mg/kg), and S group (MCT 60 mg/kg plus 10 mg/kg/day simvastatin by gavage during 28 days). Body weight, right ventricular pressure and right ventricular/left ventricle+septum ratio in each group were measured. The rats were sacrificed after 28 days. Total RNA was extracted from the rat heart tissue and microarray analysis was performed. RESULTS: Administration of simvastatin significantly inhibited the progression of right ventricular hypertrophy at day 28 in the S group than in the M group. Compared with the C group, MCT was associated with a significant difference in expression of genes related to biosynthesis and with the regulation of heart contraction rate. Simvastatin treatment resulted in a significantly changed expression of genes about the regulation of progression through cell cycle and system development compared to the M group. The expressions of nitric oxide synthase and brain natriuretic peptide were significantly decreased after simvastatin treatment. CONCLUSION: Administration of simvastatin exerted inhibitory effects on right ventricular hypertrophy during the development of MCT-induced pulmonary arterial hypertension in rats. Simvastatin changes the expression of genes associated with various functions.
Animals ; Apoptosis ; Body Weight ; Cell Cycle ; Gene Expression ; Heart* ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Hypertension ; Hypertension, Pulmonary ; Hypertrophy, Right Ventricular ; Male ; Microarray Analysis* ; Monocrotaline ; Myocytes, Smooth Muscle ; Natriuretic Peptide, Brain ; Nitric Oxide Synthase ; Rats* ; RNA ; Simvastatin* ; Ventricular Pressure