[Platelet factor 4 and ß-thromboglobulin in blood plasma of patients with acute exacerbation of chronic obstructive pulmonary disease].

OBJECTIVE: To explore the role of platelet factor 4 (PF4) and ß-thromboglobulin (ß-TG) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). METHODS: A total of 71 AECOPD patients and 50 chronic obstructive pulmonary disease (COPD) patients within a stable stage were admitted into Beijing Chaoyang Hospital from January 2008 to June 2010. And another 40 healthy volunteers were selected as control group. The data of demographics, arterial blood gas analysis and pulmonary function parameters was collected and analyzed. The plasma levels of PF4 and ß-TG were measured by enzyme-linked immunosorbent assay (ELISA). Platelet count was measured by hematology analyzer. Statistical analysis was used for PF4, ß-TG and platelet count. Spearman rank correlation was used for correlation analysis. RESULTS: No differences in age and gender existed among the AECOPD, stable and control groups. The plasma level of PF4 in the AECOPD group (2.28 µg/L) was significantly higher than that of the stable group (2.01 µg/L) and control group (1.57 µg/L) (both P < 0.05). The level of ß-TG in AECOPD was 2.32 µg/L and it was significantly higher than that of the stable group (1.85 µg/L) and control group (1.29 µg/L) (both P < 0.05). The differences in platelet counts were insignificant between the AEC OPD group ((196 ± 67) ×10(9)/L), stable group ((194 ± 50) ×10(9)/L) and control group ((190 ± 48) ×10(9)/L). AECOPD group was divided into moderate, severe and very severe groups by pulmonary function parameters. The levels of PF4 and ß-TG in very severe group were significantly higher than those in moderate and severe groups (P < 0.05). A significant positive correlation was observed between PF4 and ß-TG (r = 0.518, P < 0.01). The levels of PF4 and ß-TG were negatively correlated with FEV1%, FEV1/FVC and PaO2 (all P < 0.05). CONCLUSION: Abnormal platelet activation exists in AECOPD. And the levels of PF4 and ß-TG may reflect the severity of AECOPD and can be used as the markers of estimating prethrombotic state.

Evaluation of black carbon source apportionment based on one year's daily observations in Beijing.

Combustion-derived black carbon (BC) is increasingly recognized as a significant pollutant that can have adverse effects on the atmospheric environment, human health, and regional climate. Fossil fuel combustion is the main source of BC, yet understanding of the relative contributions to BC from coal and liquid fuel combustion remains incomplete. Moreover, few studies have assessed the relative contributions based on long-term continuous daily field observations. This study adopted a Bayesian model of a three-dimensional array of a stable carbon isotope and the ratios of non-sea-salt K+ to BC and ΔBC/ΔCO of one year's daily observations (from September 1, 2017 to August 31, 2018) to constrain source apportionment of BC in Beijing (China). Results showed that both the BC and the carbon isotope concentrations exhibited strong seasonal variability, and that the annual BC concentration has decreased significantly in recent years. The Bayesian model results also revealed that the relative contributions from the combustion of coal, liquid fuel, and biomass were 42% ± 18%, 42% ± 18%, and 16% ± 11%, respectively, with a larger contribution from coal (liquid fuel) combustion in winter and spring (summer and autumn). The seasonal variation of source appointment was attributed to local and regional fuel combustion coupled with meteorological conditions. With increasing PM2.5 level, the BC concentration derived from biomass burning increased fastest, followed by that derived from coal combustion. But concentration of secondary inorganic ions increased faster than BC as PM2.5 increased.

Enhanced biomass burning as a source of aerosol ammonium over cities in central China in autumn.

Atmospheric ambient gaseous ammonia (NH3), the most abundant alkaline gas, affects public health and climate change through its key role in the formation of secondary aerosols via reactions with acidic gases. Estimation of the contributions of ammonia sources is very challenging in the urban atmosphere. Stable nitrogen isotope ratio (δ15N) measurements have shown that urban aerosol NH4+ and gaseous NH3 are derived from fossil fuel combustion-related (FF) sources, such as coal combustion, NH3 slip, and vehicle exhaust, and volatilization-related sources, such as agriculture and urban water volatilization. Biomass burning (BB) sources, especially residential biofuel, can produce vast quantities of NH3 and other pollutants and may greatly influence air quality and contribute to increased urban NH3 emissions. In the present study, we continually collected PM2.5 samples at three urban sites in Central China during autumn and analyzed the major water-soluble ions and δ15N values of aerosol NH4+. The concentrations of NH4+ increased as the temperature decreased close to winter, whereas the δ15N values did not show this pattern. According to the Bayesian model after isotope fractionation correction, FF sources contributed to 56.4 ± 17.1%, 46.4 ± 18.2%, and 51.8 ± 14.9% of aerosol NH4+ in Nanchang, Wuhan, and Changsha, respectively, throughout autumn. The contributions from BB sources were 34.5 ± 20.4%, 46.4 ± 21.4%, and 40.4 ± 17.4% for Nanchang, Wuhan, and Changsha, respectively. We also found the fraction of aerosol NH4+ from BB increased in all three cities from September to November 2017, which was likely caused by increased heating demands with the decrease in temperature during the season. Furthermore, BB was responsible for a severe haze event (maximum PM2.5 of 205.69 µg/m3) in Nanchang. These findings suggest government controls to improve air quality should include BB sources in addition to FF sources.

Social defeat stress promotes tumor growth and angiogenesis by upregulating vascular endothelial growth factor/extracellular signal-regulated kinase/matrix metalloproteinase signaling in a mouse model of lung carcinoma.

Numerous epidemiological and experimental animal studies have indicated that chronic psychological stress may promote tumor development. However, the underlying molecular mechanisms by which chronic stress promotes tumorigenesis remain to be fully elucidated and animal models have not yet been well established. In the present study, an established mouse model of repeated social defeat stress (RSDS), was generated and used to investigate the effect of stress on tumor growth and metastasis. C57BL/6 mice were exposed to RSDS for 10 days, followed by subcutaneousl inoculation with Lewis lung carcinoma cells for seven days. The tumor weight and volume as well as the number of the lung metastatic nodules were then determined. Vascular endothelial growth factor (VEGF) serum levels were measured using ELISAs. In addition, expression levels of VEGF receptor (VEGFR) and L1 cell adhesion molecule (L1CAM) messenger (m)RNA were confirmed using reverse transcription quantitative polymerase chain reaction. Furthermore, protein expression levels of phosphorlyated extracellular signal-regulated kinase (pERK), matrix metalloproteinase (MMP)-2 and MMP-9 were examined using western blot analysis. The results showed that RSDS significantly increased the weight and the volume of the primary tumor as well as the number of the lung metastatic nodules. Serum VEGF levels were significantly higher in the tumor-stress group compared with those of the unstressed tumor mice. In addition, tumors in stressed animals demonstrated markedly enhanced expression of VEGFR-2 and L1CAM mRNA as well as pERK, MMP-2 and MMP-9 protein expression. In conclusion, these results suggested that RSDS contributed to lung cancer progression, angiogenesis and metastasis, which was partially associated with increased VEGF secretion and therefore the activation of the ERK signaling pathway, resulting in the induction of MMP-2 and MMP-9 protein expression.

Molecular mechanism of icariin on rat asthmatic model.

BACKGROUND: Effects of icariin on airway inflammation in asthmatic rats and the intervention of LPS induced inflammation are interfered with the machanism of icariin. Our study aimed to observe the effect of icariin on ovalbumin-induced imbalance of Th1/Th2 cytokine expression and its mechanism. METHODS: Sixty male SD rats were randomly divided into control group (PBS), asthma group (ovalbumin (OVA)-induced), dexamethasone group, and OVA+icariin low, medium and high dose groups (5, 10, 20 mg/kg, respectively). Each group had ten rats. The model of OVA sensitization was a rat asthma model. Enzyme-linked immunosorbent assay (ELISA) method was used to observe the effects of icariin on interleukin-4 (IL-4) and inerferon γ (IFN-γ) in rats' lung tissue. Immunohistochemical staining was applied to detect the intervention effects of icariin on T cells (T-bet) and gatabinding protein 3 (GATA-3) in rat pulmonary tissue. Realtime RT-PCR was used to observe the intervention effects of icariin on T-bet and GATA-3 mRNA expression in rat pulmonary tissue and spleen lymphocytes. Western blotting was used to observe the icariin intervention effects on T-bet, GATA-3 and nuclear factor-Kappa B (NF-κB) p65 protein expressions in rat pulmonary tissue. RESULTS: The ELISA results from pulmonary tissue showed that IL-4 expression was significantly reduced (P < 0.05), while the IFN-γ expression increased but not significantly when we compared OVA+icariin medium and high dose groups with the asthma group. Immunohistochemical staining of pulmonary tissue showed that the GATA-3 decreased significantly while the T-bet staining did not change in the OVA+icariin high dose group. In pulmonary tissue and spleen lymphocytes T-bet and GATA-3 mRNA expressions were significantly reduced (P < 0.05) in icariin treatment groups compared with the asthma model group. GATA-3 and T-bet mRNA in rat spleen lymphocytes in the asthma group were higher than in the control group. GATA-3 mRNA expression in pulmonary tissue significantly decreased (P < 0.05) while T-bet mRNA expression decreased but not significantly in the icariin treatment group compared with the asthma group. T-bet and GATA-3 protein expressions in pulmonary tissue increased significantly compared with the asthma group, which meant that icariin could inhibit the increase of GATA-3 protein, but not of T-bet. The bronchus, blood vessels and periphery pulmonary tissue had infiltration of inflammatory cells in the OVA+icariin high dose group while NF-κB p65 cells were reduced, and expression of NF-κB p65 in this group was less than in the asthma group. The expression of total p65 protein decreased with icariin treatment while the expression of cytoplasmic p65 protein increased. CONCLUSIONS: Icariin could regulate the imbalance of Th1/Th2 cytokines in asthmatic rat pulmonary tissue. Icariin could regulate the imbalance of Th1/Th2 associated transcription factors T-bet and GATA-3 in asthmatic rat pulmonary tissue and spleen lymphocytes. Icariin could inhibit the activation of NF-κB p65 protein in asthmatic rat pulmonary tissue.

Induction of renal 20-hydroxyeicosatetraenoic acid by clofibrate attenuates high-fat diet-induced hypertension in rats.

This study compared renal hemodynamics, the expression of CYP4A isoforms [the enzymes for 20-hydroxyeicosatetraenoic acid (20-HETE) production], and tubular sodium transporters in male rats fed a high-fat (HF) or control diet for 10 weeks. We also studied the effect of treatment with clofibrate, a CYP4A inducer, on sodium retention and renal function and on CYP4A expression in HF rats. HF rats had higher blood pressure (BP), renal plasma flow, and glomerular filtration rate (GFR), but no significant change in renal vascular resistance. Reverse transcription-polymerase chain reaction analysis showed that CYP4A1 and CYP4A8 expression was significantly decreased in the renal cortex of HF rats. Western blot analysis showed up-regulation of expression of the alpha-subunit of the epithelial sodium channel (alpha-ENaC), the beta-subunit of the epithelial sodium channel (beta-ENaC), sodium/hydrogen exchanger (NHE)-3, and the renal outer medulla K(+) channel (ROMK) in HF rats, whereas expression of the gamma-subunit of the epithelial sodium channel and the alpha1-subunit of Na(+)-K(+)-ATPase remained unchanged. Thus, HF treatment caused the reduction of renal CYP4A1 and CYP4A8 expression, whereas the increases in alpha-ENaC, beta-ENaC, NHE-3, and ROMK expression in renal tubules may have contributed sodium retention and hypertension in HF rats. Furthermore, clofibrate treatment (240 mg/kg/day) caused the decrease of BP and GFR and the attenuation of cumulative sodium balance in HF rats. The attenuation of sodium retention by clofibrate treatment is linked to decreased expression of NHE-3 in renal cortex. Clofibrate induction of CYP4A expression occurred in proximal tubules and in the thick ascending limb of the loop of Henle but not in renal microvessels. This induction correlated with the expression of peroxisome proliferator-activated receptor (PPARalpha) in renal tubules. Therefore, these results suggest that the effects of clofibrate on sodium retention and blood pressure regulation in HF rats may be due to the induction of renal tubular 20-HETE production through the PPARalpha pathway.