Essential role of lattice oxygen in hydrogen sensing reaction.

Understanding the sensing mechanism of metal oxide semiconductors is imperative to the development of high-performance sensors. The traditional sensing mechanism only recognizes the effect of surface chemisorbed oxygen from the air but ignores surface lattice oxygen. Herein, using in-situ characterizations, we provide direct experimental evidence that the surface chemisorbed oxygen participated in the sensing process can come from lattice oxygen of the oxides. Further density functional theory (DFT) calculations prove that the p-band center of O serves as a state of art for regulating the participation of lattice oxygen in gas-sensing reactions. Based on our experimental data and theoretical calculations, we discuss mechanisms that are fundamentally different from the conventional mechanism and show that the easily participation of lattice oxygen is helpful for the high response value of the materials.

Evaluating the therapeutic potential of moxibustion on polycystic ovary syndrome: a rat model study on gut microbiota and metabolite interaction.

Polycystic ovary syndrome (PCOS) is a common systemic disorder related to endocrine disorders, affecting the fertility of women of childbearing age. It is associated with glucose and lipid metabolism disorders, altered gut microbiota, and insulin resistance. Modern treatments like pioglitazone, metformin, and spironolactone target specific symptoms of PCOS, while in Chinese medicine, moxibustion is a common treatment. This study explores moxibustion's impact on PCOS by establishing a dehydroepiandrosterone (DHEA)-induced PCOS rat model. Thirty-six specific pathogen-free female Sprague-Dawley rats were divided into four groups: a normal control group (CTRL), a PCOS model group (PCOS), a moxibustion treatment group (MBT), and a metformin treatment group (MET). The MBT rats received moxibustion, and the MET rats underwent metformin gavage for two weeks. We evaluated ovarian tissue changes, serum testosterone, fasting blood glucose (FBG), and fasting insulin levels. Additionally, we calculated the insulin sensitivity index (ISI) and the homeostasis model assessment of insulin resistance index (HOMA-IR). We used 16S rDNA sequencing for assessing the gut microbiota, 1H NMR spectroscopy for evaluating metabolic changes, and Spearman correlation analysis for investigating the associations between metabolites and gut microbiota composition. The results indicate that moxibustion therapy significantly ameliorated ovarian dysfunction and insulin resistance in DHEA-induced PCOS rats. We observed marked differences in the composition of gut microbiota and the spectrum of fecal metabolic products between CTRL and PCOS rats. Intriguingly, following moxibustion intervention, these differences were largely diminished, demonstrating the regulatory effect of moxibustion on gut microbiota. Specifically, moxibustion altered the gut microbiota by increasing the abundance of UCG-005 and Turicibacter, as well as decreasing the abundance of Desulfovibrio. Concurrently, we also noted that moxibustion promoted an increase in levels of short-chain fatty acids (including acetate, propionate, and butyrate) associated with the gut microbiota of PCOS rats, further emphasizing its positive impact on gut microbes. Additionally, moxibustion also exhibited effects in lowering FBG, testosterone, and fasting insulin levels, which are key biochemical indicators associated with PCOS and insulin resistance. Therefore, these findings suggest that moxibustion could alleviate DHEA-induced PCOS by regulating metabolic levels, restoring balance in gut microbiota, and modulating interactions between gut microbiota and host metabolites.

Loading dose vitamin D3 improves vitamin D insufficiency in adults undergoing hematopoietic stem cell transplantation: A randomized controlled trial.

Allogeneic hematopoietic stem cell transplant (aHSCT) patients are well known to be at high risk of vitamin D (vit D) deficiency. This study assessed whether a loading dose (100,000 IU) of vitamin D3 pre-aHSCT could effectively achieve and maintain sufficient post-transplant vit D levels (serum total 25 hydroxy vitamin D (25(OH)D) ≥ 75nmol/L). Dual-energy X-ray absorptiometry (DXA) was also conducted for bone health evaluation. 74 patients were enrolled and randomly assigned, in a 1:1 ratio, either to the high vit D group (single loading dose (100,000 IU) plus 2,000 IU vit D3 daily) or the control group (2,000 IU vit D3 daily). Vit D levels were measured at three time points (baseline, day 30 and day 100 post-aHSCT). At baseline, fewer than 50% patients had a sufficient 25(OH)D (control: 42.9%; high vit D: 43.6%). The proportion of patients with sufficient 25(OH)D (nmol/L) was increased at day 30 and day 100, with a trend of higher proportion in the high vit D group at day 30 (high vit D vs. control: 89.7% vs. 74.3%, p = 0.08). The increased 25(OH)D was significantly higher in the high vit D group at day 30 (high vit D vs. control: 29±25.2 vs. 14 ±21.9, p = 0.01). Insufficient vit D level before transplant (baseline) was an independent risk factor for vit D insufficiency (serum 25(OH)D < 75nmol/L) post-aHSCT (OR = 4.16, p = 0.03). DXA suggested significant bone loss for total hip in both groups, and in the femoral neck for the control group only. In conclusion, single loading dose vitamin D3 significantly increased total 25(OH)D levels at day 30 post-transplant, and the intervention was especially beneficial for patients with baseline vit D insufficiency. We acknowledge that the primary outcome at day 100 post-aHSCT indicating superiority of loading dose versus daily dose supplementation was not met.

Effect of freeze-thaw cycles on the physicochemical properties and frying performance of frozen Youtiao dough.

The impact of freeze-thaw cycles on the physicochemical properties and frying performance of frozen Youtiao dough with chemical leavening agent was investigated. The specific volume of Youtiao made from frozen dough decreased by 66% after 4 freeze-thaw cycles. Meanwhile, the hardness and puncture force showed increasing trends, and the fibrous structure became unclear. The extensibility, storage modulus (G') and loss modulus (G'') of frozen Youtiao dough decreased during freeze-thaw cycles, while the creep compliance increased. Changes in rheological properties demonstrated that frozen Youtiao dough was more deformable and its strength was weakened. Moreover, the sodium dodecyl sulfate (SDS) extractable protein and free sulfhydryl content increased, revealing that protein was depolymerized. The loose structure with large pores and fractured protein network were observed by micromorphology. Freeze-thaw cycles had a detrimental effect on the Youtiao quality, which was related to the deterioration of rheological properties and protein structure of frozen Youtiao dough.

From inequalities involving exponential functions and sums to logarithmically complete monotonicity of ratios of gamma functions.

In this paper, the authors review origins, motivations, and generalizations of a series of inequalities involving finitely many exponential functions and sums. They establish three new inequalities involving finitely many exponential functions and sums by finding convexity of a function related to the generating function of the Bernoulli numbers. They also survey the history, backgrounds, generalizations, logarithmically complete monotonicity, and applications of a series of ratios of finitely many gamma functions, present complete monotonicity of a linear combination of finitely many trigamma functions, construct a new ratio of finitely many gamma functions, derive monotonicity, logarithmic convexity, concavity, complete monotonicity, and the Bernstein function property of the newly constructed ratio of finitely many gamma functions. Finally, they suggest two linear combinations of finitely many trigamma functions and two ratios of finitely many gamma functions to be investigated.

Alkali metal-incorporated spinel oxide nanofibers enable high performance detection of formaldehyde at ppb level.

Sensing material with high sensitivity, excellent selectivity and ultra-low detection limit is crucial for monitoring formaldehyde, which is a kind of hazardous gas to human health at very low concentration. Some one-dimensional semiconductor metal oxides show acceptable responses towards formaldehyde. However, the detection limit and selectivity of these sensors are still not satisfied, especially at ppb level. Herein, alkali metals (K, Na) doped CdGa2O4 nanofibers with excellent formaldehyde sensing performance are prepared by an electrospinning method. These nanofibers have been characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HRTEM), electron paramagnetic resonance spectroscopy (EPR), elemental mapping and other techniques. As a result, the sensor based on 7.5 at.% K doped CdGa2O4 gives remarkably improved formaldehyde sensing properties compared with that of pristine CdGa2O4. The greatly increased sensitivity and selectivity should be attributed to the increased chemisorbed oxygen and the enhanced basicity caused by the additional alkali metal, respectively. All in all, the 7.5 at.% K doped CdGa2O4 is a good candidate for the rapid detecting formaldehyde at ppb level.

Knockdown of lncRNA HCP5 Suppresses the Progression of Colorectal Cancer by miR-299-3p/PFN1/AKT Axis.

BACKGROUND: Colorectal cancer (CRC) is one of the most common malignant tumors in the digestive system. The lncRNA HCP5 has been reported to affect the progression of tumor in several types of cancer. Here, in this research, we focus on the role and function of lncRNA HCP5 in human colorectal cancer. MATERIALS AND METHODS: Tissue samples from colorectal cancer patients were used for detecting the expression of HCP5 by qRT-PCR. Proliferation, migration, invasion and apoptotic cells were assessed by CCK-8, colony formation, transwell assays and flow cytometry in SW480 and HCT-116 cells. The interactions between miR-299-3p and HCP5 or PFN1 were analyzed and confirmed by online database and luciferase reporter assays. The changes in PFN1 and AKT proteins were measured by Western blot. In vivo experiment was used to confirm the role of HCP5 in CRC. RESULTS: The expression of HCP5 had a higher level in colorectal cancer samples and cells by qRT-PCR, comparing with the normal colorectal tissues and human normal colon epithelial cell. It was revealed that knockdown of HCP5 inhibited viabilities, migration and invasion, while inducing apoptosis in SW480 and HCT-116 cells. Then, HCP5 negatively regulated the expressions of miR-299-3p, which negatively regulated the expressions of PFN1 by targeting PFN1. Furthermore, miR-299-3p inhibitor could alleviate the inhibiting effect by si-HCP5 on cell process of SW480 and HCT-116 cells. In addition, the lncHCP5/miR-299-3p/PFN1 axis could affect the progression of CRC through activating the AKT signaling. Last, we confirmed that knockdown of HCP5 inhibited the progression of CRC with an in vivo experiment. CONCLUSION: The experiments and analyses support our hypothesis that knockdown of lncRNA HCP5 suppresses the progression of colorectal cancer by miR-299-3p/PFN1/AKT axis.

Effect of Depth of Electroacupuncture on the IPSS of Patients with Benign Prostatic Hyperplasia.

This study aimed to evaluate the efficacy of electroacupuncture (EA) on Ciliao (BL 32) and Zhongliao (BL 33) acupoints at different depths for the treatment of benign prostatic hyperplasia (BPH) through a single-blind randomized controlled trial. All 120 patients diagnosed with BPH were randomly allocated to an experimental group (deep insertion group, DI group, n = 60) and control group (shallow insertion group, SI group, n = 60) 3 times a week for 4 weeks. The observed results included the International Prostate Symptom Score (IPSS), Quality of Life score (QOL), maximum urine flow rate (Qmax), and postvoid residual urine volume (PVR). After treatment, at both depths, the BPH symptoms of patients were improved by EA. There were significant differences between the IPSS, QOL, and the effective rate of the experimental group and the control group (P < 0.05). Although the observed PVR and Qmax were better than those before treatment, there was no statistical significance between two groups (P > 0.05). Thus, EA with deep insertion can effectively improve the patients' urinary symptoms and quality of life, and it will be suitable for clinical application.

A theoretical study of the inhibition effect of PAMAM molecule on silica scale.

In this work, the molecular modeling method was performed to study adsorption interaction between PAMAM molecules of different generations and silicic acid molecules, and the inhibition effect on silica scale were discussed. The results show that adsorption energies of PAMAM molecule of generation 1.0 with amine-terminated groups are stronger than those of generation 1.5 with terminated carboxyl group. The composition of adsorption interactions are the dominating electrostatic interactions and van de Waals interactions as well as H-bond interactions. It is qualitatively discussed that the inhibition effect of generation 1.0 on silica scale is stronger than that of generation 1.5 in the neutral solution.

Design of Pore Size and Functionality in Pillar-Layered Zn-Triazolate-Dicarboxylate Frameworks and Their High CO2/CH4 and C2 Hydrocarbons/CH4 Selectivity.

In the design of new materials, those with rare and exceptional compositional and structural features are often highly valued and sought after. On the other hand, materials with common and more accessible modes can often provide richer and unsurpassed compositional and structural variety that makes them a more suitable platform for systematically probing the composition-structure-property correlation. We focus here on one such class of materials, pillar-layered metal-organic frameworks (MOFs), because different pore size and shape as well as functionality can be controlled and adjusted by using pillars with different geometrical and chemical features. Our approach takes advantage of the readily accessible layered Zn-1,2,4-triazolate motif and diverse dicarboxylate ligands with variable length and functional groups, to prepare seven Zn-triazolate-dicarboxylate pillar-layered MOFs. Six different gases (N2, H2, CO2, C2H2, C2H4, and CH4) were used to systematically examine the dependency of gas sorption properties on chemical and geometrical properties of those MOFs as well as their potential applications in gas storage and separation. All of these pillar-layered MOFs show not only remarkable CO2 uptake capacity, but also high CO2 over CH4 and C2 hydrocarbons over CH4 selectivity. An interesting observation is that the BDC ligand (BDC = benzenedicarboxylate) led to a material with the CO2 uptake outperforming all other metal-triazolate-dicarboxylate MOFs, even though most of them are decorated with amino groups, generally believed to be a key factor for high CO2 uptake. Overall, the data show that the exploration of the synergistic effect resulting from combined tuning of functional groups and pore size may be a promising strategy to develop materials with the optimum integration of geometrical and chemical factors for the highest possible gas adsorption capacity and separation performance.

Systemic and vascular effects of circulating diesel exhaust particulate matter.

OBJECTIVE: Numerous studies have found an association between transiently increased particulate matter air pollution and acute adverse cardiovascular health effects; however, the mechanisms underlying these effects are not clear. Translocation of ultra-fine ambient particulate matter has been proposed to play a key role in these acute side effects. This study was designed to determine the contribution of circulating (translocated) diesel exhaust particles (DEPs) to the systemic and vascular effects. METHODS: C57 mice (10-week) received intravenous DEPs via tail vein injection. Following 1-h post-injection, inflammatory cytokines (IL-1ß, IL-6 and TNF-α), peripheral blood cell counts, band cell counts, aortic endothelial function and vascular constriction were assessed. Thoracic aortae were isolated, and endothelial function was examined by measuring acetylcholine (ACh) and sodium nitroprusside (SNP)-stimulated vascular relaxation using a wire myograph. In addition, phenylephrine (PE)-stimulated vasoconstriction was also measured. The amount of DEPs deposited and trapped in tissues (the spleen, liver, lungs and heart) were quantified. RESULTS: Acute systemic DEP exposure caused a significant increase in TNF-α, peripheral neutrophil and band cell counts. ACh and SNP-induced relaxation were not affected by acute systemic DEP exposure, neither was PE-stimulated constriction. There was a significantly increased DEP deposition in the spleen as well as in the liver. No significantly increased DEPs were detected in the lung and heart. CONCLUSION: Here we show that circulating DEPs induce a systemic response characterized by increased TNF-α, peripheral granulocytes, but does not impact endothelial function. Our study also suggests that circulating particles are rapidly removed from the circulation and predominantly sequestered in the spleen and liver.

Statins attenuate the development of atherosclerosis and endothelial dysfunction induced by exposure to urban particulate matter (PM10).

Exposure to ambient air particulate matter (particles less than 10µm or PM10) has been shown to be an independent risk factor for the development and progression of atherosclerosis. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have well-established anti-inflammatory properties. The aim of this study was to determine the impact of statins on the adverse functional and morphological changes in blood vessels induced by PM10. New Zealand White rabbits fed with a high fat diet were subjected to balloon injury to their abdominal aorta followed by PM10/saline exposure for 4weeks±lovastatin (5mg/kg/day) treatment. PM10 exposure accelerated balloon catheter induced plaque formation and increased intimal macrophages and lipid accumulation while lovastatin attenuated these changes and promoted smooth muscle cell recruitment into plaques. PM10 impaired vascular acetylcholine (Ach) responses and increased vasoconstriction induced by phenylephrine as assessed by wire myograph. Supplementation of nitric oxide improved the impaired Ach responses. PM10 increased the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in blood vessels and increased the plasma levels of endothelin-1 (ET-1). Incubation with specific inhibitors for iNOS, COX-2 or ET-1 in the myograph chambers significantly improved the impaired vascular function. Lovastatin decreased the expression of these mediators in atherosclerotic lesions and improved endothelial dysfunction. However, lovastatin was unable to reduce blood lipid levels to the baseline level in rabbits exposed to PM10. Taken together, statins protect against PM10-induced cardiovascular disease by reducing atherosclerosis and improving endothelial function via their anti-inflammatory properties.

Statins reduce ambient particulate matter-induced lung inflammation by promoting the clearance of particulate matter, < 10 µm from lung tissues.

BACKGROUND: The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) suppress ambient particulate matter, 10 µm (PM(10) )-induced inflammatory response in vitro. The aim of this study was to determine the effect of statins on PM(10) -induced lung inflammation in vivo. METHODS: New Zealand white rabbits were exposed to either PM(10) (1.0 mg/kg) or saline by direct intratracheal instillation three times a week for 4 weeks lovastatin 5.0 mg/kg/d. BAL fluid was assessed for cell counts and proinflammatory cytokine levels. Lung inflammation was quantified using immunohistochemical techniques and morphometric methods. Ex vivo phagocytosis assay of alveolar macrophages using PM 10 particles was performed. Distribution of PM(10) particles in lung tissues and draining lymph nodes was quantified morphometrically to evaluate the clearance of PM(10) particles. RESULTS: PM(10) exposure increased the production of IL-6 and IL-8, promoted the recruitment of macrophages and polymorphonuclear leukocytes into the lung, and activated these recruited leukocytes. Lovastatin significantly suppressed all these effects. Lovastatin increased the phagocytic activity of macrophages and promoted the migration of PM 10 -laden macrophages to the regional lymph nodes. CONCLUSIONS: Lovastatin attenuates the PM(10) -induced recruitment and activation of alveolar macrophages and polymorphonuclear leukocytes, reduces local proinflammatory cytokine production, and promotes the clearance of PM(10) particles from lung tissues to regional lymph nodes. These novel pleiotropic properties of statins are most likely to contribute to the downregulation of PM(10) -induced lung inflammation.

Exposure to diesel exhaust upregulates COX-2 expression in ApoE knockout mice.

INTRODUCTION: We have shown that diesel exhaust (DE) inhalation caused progression of atherosclerosis; however, the mechanisms are not fully understood. We hypothesize that exposure to DE upregulates cyclooxygenase (COX) expression and activity, which could play a role in DE-induced atherosclerosis. METHODS: ApoE knockout mice (30-week old) fed with regular chow were exposed to DE (at 200 µg/m(3) of particulate matter) or filtered air (control) for 7 weeks (6 h/day, 5 days/week). The protein and mRNA expression of COX-1 and COX-2 were evaluated by immunohistochemistry analysis and quantitative real-time PCR, respectively. To examine COX activity, thoracic aortae were mounted in a wire myograph, and phenylephrine (PE)-stimulated vasoconstriction was measured with and without the presence of COX antagonists (indomethacin). COX-2 activity was further assessed by urine 2,3-dinor-6-keto PGF(1α) level, a major metabolite of prostacyclin I(2) (PGI(2)). RESULTS: Immunohistochemistry analysis demonstrates that DE exposure enhanced COX-2 expression in both thoracic aorta (p < 0.01) and aortic root (p < 0.03), with no modification of COX-1 expression. The increased COX-2 expression was positively correlated with smooth muscle cell content in aortic lesions (R(2) = 0.4081, p < 0.008). The fractional changes of maximal vasoconstriction in the presence of indomethacin was attenuated by 3-fold after DE exposure (p < 0.02). Urine 2,3-dinor-6-keto PGF(1α) level was 15-fold higher in DE group than the control (p < 0.007). The mRNA expression of COX-2 (p < 0.006) and PGI synthase (p < 0.02), but not COX-1, was significantly augmented after DE exposure. CONCLUSION: We show that DE inhalation enhanced COX-2 expression, which is also associated with phenotypic changes of aortic lesion.

Novel properties of statins: suppression of the systemic and bone marrow responses induced by exposure to ambient particulate matter (PM(10)) air pollution.

Exposure to ambient particulate matter (PM(10) elicits systemic inflammatory responses that include the stimulation of bone marrow and progression of atherosclerosis. The present study was designed to assess the effect of repeated exposure of PM(10) on the turnover and release of polymorphonuclear leukocytes (PMNs) from the bone marrow into the circulation and the effect of lovastatin on the PM(10)-induced bone marrow stimulation. Rabbits exposed to PM(10)three times a week for 3 wk, were given a bolus of 5'-bromo-2'-deoxyuridine to label dividing cells in the marrow to calculate the transit time of PMNs in the mitotic or postmitotic pool. PM(10) exposure accelerated the turnover of PMNs by shortening their transit time through the marrow (64.8 ± 1.9 h vs. 34.3 ± 7.4 h, P < 0.001, control vs. PM(10)). This was predominantly due to a rapid transit of PMNs through the postmitotic pool (47.9 ± 0.7 h vs. 21.3 ± 4.3 h, P < 0.001, control vs. PM(10)) but not through the mitotic pool. Lovastatin delayed the transit time of postmitotic PMNs (38.2 ± 0.5 h, P < 0.001 vs. PM(10)) and shifted the postmitotic PMN release peak from 30 h to 48 h. PM(10) exposure induced the prolonged retention of newly released PMNs in the lung, which was reduced by lovastatin (P < 0.01). PM(10) exposure increased plasma interleukin-6 levels with significant reduction by lovastatin (P < 0.01). We conclude that lovastatin downregulates the PM(10)-induced overactive bone marrow by attenuating PM(10)-induced systemic inflammatory responses.

Diesel exhaust inhalation induces heat shock protein 70 expression in vivo.

Exposure to urban air pollution is an independent risk factor for increased cardiovascular diseases. Heat shock protein 70 (HSP70) has been implicated in the pathogenesis of vascular dysfunction and cardiovascular diseases. This study has been designed to determine whether inhalation of urban air induces HSP70 expression in the lung and blood as well as the association of HSP70 and air pollution-induced vascular dysfunction. Apolipoprotein E (Apo-E) deficient mice were exposed to diesel exhaust (DE) either acutely (3 days, 200 or 400 µg/m(3) for 6 h/day) or chronically (7 weeks, 200 or 400 µg/m(3) for 6 h/day). HSP70 was measured in the lung using immunohistochemistry, and in the plasma by ELISA. Abdominal aorta rings were used to determine vascular functional responses. Chronic DE-exposure increased the fraction of HSP70 positive alveolar macrophages (AM) that was related to the fraction of particle-laden AM in the lung (r(2) = 0.48, p <0.01). Chronic DE-exposure increased plasma HSP70 levels and reduced blood vessel responses to phenylephrine (PE). The fraction of particle-laden HSP70 positive AM was associated with abnormal vasoconstriction responses to PE induced by DE-exposure (r(2) = 0.12, p = 0.02). Our results show that chronic inhalation of DE increases HSP70 expression in the lung and systemic circulation, and we postulate that HSP70 possibly contributes to air pollution induced vascular dysfunction and cardiovascular diseases.

Endotoxin-induced cardiovascular dysfunction in mice: effect of simvastatin.

Lung infections are associated with acute lung injury (ALI), systemic inflammation, and vascular events. Clinical studies suggest that statins improve health outcomes of patients with pneumonia and ALI. The mechanisms by which this occurs are unknown. The aim of this study was to determine whether statins attenuate systemic inflammation and cardiovascular dysfunction related to ALI in mice. Simvastatin (SS; 20 mg/kg) or vehicle solution was instilled intraperitoneally into mice 24 h before and again just prior to intratracheal LPS instillation (1 µg/g). These mice were then anesthetized with 2.0% isoflurane and underwent a short surgical procedure to instill LPS. Four hours later, IL-6 levels in bronchoalveolar lavage fluid and in arterial and venous serum were measured. Cardiac function was evaluated using 2-D echocardiography, and endothelial function was determined using wire myography on aortic sections. LPS induced a significant increase in serum IL-6 levels. SS reduced venous (P = 0.040) but not arterial concentrations of IL-6 (P = 0.112). SS improved the maximal vasodilatory response of the aorta to ACh (P = 0.004) but not to sodium nitroprusside (P = 1.000). SS also improved cardiac output (P = 0.023). Vasodilatory response to ACh was impaired when aorta from untreated mice was incubated with ex vivo IL-6 (P = 0.004), whereas in the aorta from mice pretreated with SS, the vasodilatory response did not change with IL-6 incubation (P = 0.387). SS significantly improved LPS-induced cardiovascular dysfunction possibly by reducing systemic expression of IL-6 and its downstream signaling pathways. These findings may explain how statins improve health outcomes in patients with ALI.

Exposure to diesel exhaust up-regulates iNOS expression in ApoE knockout mice.

UNLABELLED: Traffic related particulate matter air pollution is a risk factor for cardiovascular events; however, the biological mechanisms are unclear. We hypothesize that diesel exhaust (DE) inhalation induces up-regulation of inducible nitric oxide synthase (iNOS), which is known to contribute to vascular dysfunction, progression of atherosclerosis and ultimately cardiovascular morbidity and mortality. METHODS: ApoE knockout mice (30-week) were exposed to DE (at 200 µg/m³ of particulate matter) or filtered-air (control) for 7 weeks (6 h/day, 5 days/week). iNOS expression in the blood vessels and heart was evaluated by immunohistochemistry and western blotting analysis. To examine iNOS activity, thoracic aortae were mounted in a wire myograph, and vasoconstriction stimulated by phenylephrine (PE) was measured with and without the presence of the specific inhibitor for iNOS (1400 W). NF-κB (p65) activity was examined by ELISA. The mRNA expression of iNOS and NF-κB (p65) was determined by real-time PCR. RESULTS: DE exposure significantly enhanced iNOS expression in the thoracic aorta (4-fold) and heart (1.5 fold). DE exposure significantly attenuated PE-stimulated vasoconstriction by ~20%, which was partly reversed by 1400 W. The mRNA expression of iNOS and NF-κB was significantly augmented after DE exposure. NF-κB activity was enhanced 2-fold after DE inhalation, and the augmented NF-κB activity was positively correlated with iNOS expression (R²=0.5998). CONCLUSIONS: We show that exposure to DE increases iNOS expression and activity possibly via NF-κB-mediated pathway. We suspect that DE exposure-caused up-regulation of iNOS contributes to vascular dysfunction and atherogenesis, which could ultimately lead to urban air pollution-associated cardiovascular morbidity and mortality.

Changes in atherosclerotic plaques induced by inhalation of diesel exhaust.

OBJECTIVE: Exposure to particulate matter air pollution may be an independent risk factor for cardiovascular morbidity and mortality; however, the biological mechanisms are unclear. We hypothesize that exposure to diesel exhaust (DE), an important source of traffic-related particulate air pollution, promotes changes of atherosclerotic plaque component that may lead to plaque vulnerability. METHODS AND RESULTS: 30-week old ApoE knockout mice fed with regular chow inhaled DE (at 200 µg/m(3) of particulate) or filtered-air (control) for 7 weeks (6 h/day, 5 days/week) (12 mice/group). Total number of alveolar macrophages (p<0.01) and alveolar macrophages positive for particles (p<0.0001) were more than 8-fold higher after DE inhalation than the control. DE inhalation caused 1.5 to 3-fold increases in plaque lipid content (p<0.02), cellularity (p<0.02), foam cell formation (p<0.04), and smooth muscle cell content (p<0.05). The expression of oxidative stress markers, iNOS, CD36, and nitrotyrosine was significantly increased by 1.5 to 2-fold in plaques, with enhanced systemic lipid and DNA oxidation (p<0.02). Increased foam cells and the expression of iNOS (R(2)=0.72, p=0.0081) and CD36 (R(2)=0.49, p=0.015) in plaques were positively correlated with the magnitude of DE exposure. CONCLUSIONS: Exposure to DE promotes changes in atherosclerotic plaques characteristic of unstable vulnerable plaques. Increased systemic and plaque oxidative stress markers suggest that these changes in plaques could be due to DE-induced oxidative stress.