Sulfur dioxide (SO_2) is an ordinary air pollutant globally and harm to human health. L-cysteine is the major sulfur-containing amino acid and its normal metabolism can produce hydrogen sulfur (H_2S) and SO_2. It is realized that H_2S has various bioactivities and is the third gasotransmitter after nitric oxide (NO) and carbon monoxide (CO). Recently, attention has been paid to the physiologic effects of endogenous SO_2 and its derivatives (bisulfite and sulfite) in vivo, and recognized that SO_2 and its derivatives can lower blood pressure, change heart rates, participate in inflammatory reactions, and so on, suggesting that endogenous SO_2 may modulate the physiologic functions in vivo as a bioactive molecule.

6(mmol/L).) Nicardipine(1?10~(-9) mol/L) could decrease the contraction of the rings to NE,and even could inhibit the relaxation of Na_2SO_3/NaHSO_3 almost completely.The inhibition of the endogenous SO_2 production with HDX(1?10~(-4) mol/L),resulted in an increase in the contraction of rings.The contraction curve to NE shifted to the left,and IC_(50) also changed from(6.48?0.84)?10~(-7)mol/L to(3.97?(1.63))?10~(-7) mol/L(P

Aim To investigate the effect of sulfur dioxide (SO2) on blood pressure and aortic structure of the spontaneous hypertensive rat(SHR).Methods Sixteen male SHRs at the age of 4 weeks were randomly divided into SHR control group and SHR+Na2SO3/NaHSO3 group,respectively.Another eight male WKY rats served as WKY control group.Five weeks later, the blood pressure was determined.The rat aortas were dyed with Hart's Method. The morphometric parameters including outer radius, lumen radius and the wall thickness were calculated by Leica workstation. The proliferative index (PI) of smooth muscle cells was detected by immunohistochemical assay.Results The blood pressure of SHR control increased compared with that of WKY control rats(P

Objective To investigate the production of hydrogen sulfide (H2S) in rats with monocrotaline (MCT)-induced pulmonary hypertension(PAH).Methods Fourteen male Wistar rats were randomly divided into 2 groups (7 cases for each group):control group and MCT group.Rats in the MCT group were intraperitoneally injected with MCT (60 mg/kg) on day 1 while rats in the control group received only the same volume of 9 g/L saline.And then the conventional breeding was given for 21 days.Mean pulmonary artery pressure (mPAP) was evaluated via right cardiac catheterization procedure.The ratio of right ventricular mass (RV) and left ventricular plus septal mass (LV + SP) [RV/(LV + SP)] was calculated.The morphological change of pulmonary artery was observed by applying hematoxylin-eosin (HE) staining on the lung tissue paraffin section by measuring relative media thickness (RMT) and relative media area (RMA) of pulmonary aetery.H2S contents in serum and lung tissue rat were detected by using free radicals detector.The expression of cystathionine-γ-lyase (CSE),a key enzyme catalyzing endogenous H2S generaion,in lung tissue was detected by using Western blot method.CSE mRNA level in lung was detected by adopting the real-time polymerase chain reaction (RT-PCR) method.Results Compared with control group,mPAP of rats in MCT group was increased significantly [(49.31 ±3.67) mmHg vs (14.31 ±2.07) mmHg(1 mm Hg =0.133 kPa),P ＜ 0.01] and the ratio of RV/(LV + SP) was increased (0.43 ± 0.03 vs 0.21 ± 0.03,P ＜ 0.01),while RMT and RMA of pulmonary artery were enlarged [(43.46 ± 1.94) μm vs (13.16 ± 1.48) μm,P ＜ 0.01;(3 321.10 ± 318.20) μm2 vs (963.40 ± 127.26) μm2,P ＜0.01].The evaluation of microstructure of pulmonary artery showed that the vessel wall of pulmonary artery in control rats was thin and no inflammatory cell was observed around artery.However,the vessel wall of pulmonary artery in rats of MCT group was thickened and there was evident infiltration of inflammatory cells in perivascular area.Compared with control group,H2S contents in serum and lung tissue of rats in MCT group were markedly decreased [(9.28 ± 0.94) μmol/L vs (14.20 ± 1.21) μmol/L,P ＜ 0.01;(0.43 ± 0.08) μmol/g protein vs (0.87 ±0.17) μmol/g protein,P ＜0.01],while CSE protein and mRNA expression in lung tissue of rats in MCT group were downregulated (0.14 ± 0.02 vs 0.28 ± 0.09,P ＜ 0.01;0.84 ± 0.06 vs 1.12 ± 0.04,P ＜ 0.01).Condusion Endogenous H2S pathway is significantly downregulated in rats with monocrotaline-induced pulmonary hypertension.

Objective To explore the protective effect of creatine phosphate sodium and compound coenzyme on tumor children with Adriamycin(ADM)-induced myocardial injury.Methods From Feb.2012 to Feb.2014,there were 153 tumor children administered in Shijitan Hospital,the Capital Medical University,among which there were 112 male and 41 female,aged from 10 months to 5 years,and the median age was 2.3 years.All the cases were randomly divided into 3 groups,with the dose of ADM at 20-30 mg/(m2 · d) for 3 days,and for 3 to 6 courses of treatment.All cases were rolled in the ADM chemotherapy:group A,intravenous infusion of creatine phosphate sodium(1.0 g/d) and compound coenzyme(1 injection/d),at a total of 7 days;group B with only intravenous infusion of creatine phosphate sodium(1.0 g/d) for a total of 7 days;group C with only intravenous infusion compound coenzyme(1 injection/d) for a total of 7 days.Two days before ADM chemotherapy,creatine phosphate sodium and / or compound coenzyme were administrated to protect the musculus cardiacus.One day before chemotherapy and two days after chemotherapy,the peripheral blood was taken to determine levels of malondialdehyde (MDA),creatine kinase (CK),creatine kinase MB (CK-MB),cardiac troponin(cTnT),N terminal pro-brain natriuretic peptide(NT-proBNP),high-sensitivity C-reactive protein(hsCRP),electrocardiogram,echocardiogram and so on.Then the changes of all those indicators before and after the chemotherapy between the groups were compared.Results The morbidity of myocardial damage induced by ADM was increased significantly with its dose accumulation (x2 =18.462,P ＜ 0.05).Creatine phosphate sodium combined with compound coenzyme could decrease the morbidity of myocardial damage induced by ADM (x2 =4.883,5.971,all P ＜ 0.05).Compared with those before chemotherapy,the cTnT (t =2.561,P ＜ 0.05),NT-proBNP (t =6.654,P ＜ 0.01) and hsCRP(t =3.149,P ＜ 0.01) levels of group A decreased markedly.Serum levels of MDA (t =2.170,P ＜0.05),CK-MB(t =2.596,P ＜0.05) and hsCRP(t =2.604,P ＜0.05) of group B increased obviously.Serum levels of MDA (t =2.151,P ＜ 0.05) and CK-MB (t =4.109,P ＜ 0.05) of group C also increased obviously.After chemotherapy,the detection of serum indexes of all groups showed as below.Contracted with those of group A,the serum MDA(t =4.461,P ＜ 0.01),CK-MB (t =3.273,P ＜ 0.01),cTnT (t =3.476,P ＜ 0.01),NT-proBNP (t =7.081,P ＜ 0.01) and hsCRP(t =5.941,P ＜ 0.01) levels of group B increased distinctly.Meanwhile,the MDA (t =4.064,P ＜0.01),CK-MB(t =5.452,P ＜0.01),cTnT(t =2.768,P ＜0.05),NT-proBNP(t =4.806,P ＜0.01)and hsCRP(t =3.436,P ＜ 0.05) levels of group C also increased significantly.Conclusions Both creatine phosphate and compound coenzyme could reduce the myocardial damage induced by ADM.Combination of them has important clinical value for better prevention of cardiac toxicity of ADM,enhancement of the prognosis of childhood tumor,and improvement of the long-term quality life of those children.

Objective To investigate the effects of endogenous sulfur dioxide (SO2) on the oxidative stress induced by cobalt chloride (CoCl2) in the rat pulmonary artery smooth muscle cells (PASMCs).Methods Rat PASMCs were treated with 200 μ mol/L CoCl2 to mimic the hypoxia insult.Endogenous SO2 generating enzyme aspartate aminotransferase 1 (AAT1) expression was upregulated or downregulated (AAT1 sh) by transfection with lentivirus.Rat PASMCs were randomly divided into 8 groups:vehicle group,vehicle + CoCl2 group,AAT1 group,AAT1 + CoCl2 group,scramble group,scramble + SO2 group,AAT1 sh group and AAT1 sh + SO2 group.SO2 donor Na2 SO3/NaHSO3 at concentration of 100 μ mol/L were added in scramble + SO2 group and AAT1sh + SO2 group.The expressions of AAT1,superoxide dismutase 1 (SOD1) and SOD2 in PASMCs were detected by Western blot method.In situ SO2 content in PASMCs was detected by fluorescent probe.The superoxide anions in PASMCs were labeled by dihydroethidium (DHE) probe under fluorescent microscope.Results Compared with the vehicle group,the levels of SO2 and the expressions of AAT1 (0.221 ± 0.002 vs.0.446 ± 0.004),SOD1 (0.076 ± 0.028 vs.0.171 ± 0.019) and SOD2 (0.080 ± 0.031 vs.0.196 ± 0.018) significantly decreased (all P ＜ 0.01),and superoxide anion increased in rat PASMCs of vehicle + CoCl2 group.Meanwhile,compared with vehicle + CoCl2 group,the levels of SO2 and the expressions of AAT1 (0.839 ± 0.056 vs.0.221 ± 0.002),SOD1 (0.177 ± 0.020 vs.0.076 ± 0.028) and SOD2 (0.195 ±0.018 vs.0.080-± 0.031) markedly increased (all P ＜ 0.01),and superoxide anion decreased in rat PASMCs of AAT1 + CoCl2 group.On the contrary,compared with the scramble group,the levels of SO2 and the expressions of AAT1 (0.062 ±0.017 vs.0.354 ±0.034),SOD1 (0.054 ±0.029 vs.0.157 ±0.023) and SOD2(0.180 ±0.100 vs.0.586 ± 0.176)significantly decreased (all P ＜ 0.01),and superoxide anion increased in rat PASMCs of AAT1sh group.Furthermore,compared with the AAT1 sh group,the levels of SO2 and the expressions of SOD1 (0.155 ± 0.022vs.0.054 ± 0.029) and SOD2 (0.578 ± 0.200 vs.0.180 ± 0.100) significantly increased (all P ＜ 0.01),and superoxide anion decreased in rats PASMCs of AAT1sh + SO2 group.Conclusion Endogenous SO2/AAT1 inhibits CoCl2-induced oxidative stress in rat PASMCs.

Objective To explore the changes in plasma nitric oxide (NO) and nitric oxide synthase (NOS) activity in children with orthostatic hypertension(OHT) and the relationship with blood pressure changes.Methods The OHT group included 51 children who were diagnosed OHT in in-patient and out-patient departments of Peking University First Hospital from Jun.2012 to Jun.2013.Their age range was (12 ± 2) years.At the same time,control group consisted of 28 normal children who received physical examination with their age range of(12 ± 1) years.The diagnosis of OHT was based on the clinical manifestation and head-up tests.Plasma NO was determined by using a nitrate reductase method and plasma NOS activity by a chemical colorimetric method.Results 1.There were no significant differences between OHT group and control group in age,sex ratio,height,weight and body mass index (all P ＞0.05).2.In OHT children,the upright systolic blood pressure was higher than that of the supine [(114 ± 10) mmHg vs (104 ± 9) mmHg,t =-12.853,P ＜ 0.001],and the upright diastolic blood pressure was higher than that of the supine[(73 ±7) mmHg vs(59 ± 8) mmHg,t =-21.859,P ＜0.001].3.Plasma NO level and NOS activity,however,were significantly lower in OHT group than those in the control group [NO:(28.947 ± 6.031) μmol/L vs (35.216 ±6.662) μmol/L,t =4.257,P ＜ 0.001 ; NOS activity:(14.753 ± 3.060) U/mL vs (17.560 ± 4.253) U/mL,t =3.026,P =0.006].4.There was significantly negative correlation between plasma NO and the upright systolic blood pressure(r =-0.276,P ＜ 0.05) and the systolic blood pressure change (r =-0.280,P ＜ 0.05).Conclusions Plasma NO level and NOS activity were significantly lower in OHT children than those in control group.The abnormal vascular endothelial function may play an important role in OHT in children.

Objective To investigate the effects of endogenous sulfur dioxide(SO2) on pulmonary vascular inflammation in rats with monocrotaline (MCT)-induced pulmonary hypertension.Methods Thirty-two Wistar rats were randomly divided into 4 groups(n =8 for each group):control group,MCT group,MCT + L-aspartic acid-β-hydroxamate(HDX) group,and MCT + SO2 group.Rats in the MCT group,MCT + HDX group,and MCT + SO2 group were subcutaneously injected with MCT(60 mg/kg) on the first day.For rats in MCT + HDX group,HDX(25 mg/kg,on day 0,7 and 14) was given orally after injection of MCT; and rats in MCT + SO2 group were subcutaneously injected with the SO2 donor sodium sulfite/sodium bisulfate(Na2SO3/NaHSO3,and mole ratio was adjusted to approximately 3:1) each day.Rats in the control group received only the same volume of solvent vehicle only.After 3 weeks,mean pulmonary artery pressure(mPAP) of each rat was evaluated by using a right cardiac catheterization procedure.Immunohistochemistry was used to detect the expression of inflammatory related factor intercellular adhesion molecule-1 (ICAM-1) and the key molecules of nuclear factor-κB (NF-κB) signal transduction pathway,including p65 and inhibitor of NF-κB (IκBα) in the small pulmonary artery endothelial cells.Results The differences in mPAP,expression of ICAM-1,IκBα and p65 in the small pulmonary artery endothelial cells were found among the 4 groups (mPAP:F =53.334,P ＜ 0.01 ; ICAM-1:F =183.82,P ＜ 0.01 ; IκBα:F =142.89,P ＜ 0.01 ; p65:F =105.46,P ＜0.01).The mean pulmonary artery pressure(mPAP) was significantly raised in MCT group rats as compared with that of the control group along with upregulated expressions of ICAM-1 protein and p65 protein in small pulmonary artery endothelial cells,while the expression of IκBα protein in small pulmonary artery endothelial cells was significantly low.After administration of HDX,the mPAP and the expression of ICAM-1 protein and p65 protein in small pulmonary artery endothelial cells further increased compared with those of MCT group,while the expression of IκBα protein in small pulmonary artery endothelial cells was significantly lower than that of MCT group.Whereas with treatment of SO2 derivatives,the mPAP,the expression of ICAM-1 protein and p65 protein in small pulmonary artery endothelial cells were significantly lower than those of MCT group,while the expression of IκBα protein in small pulmonary artery endothelial cells increased significantly compared with that of MCT group.Conclusions Endogenous SO2 might inhibit the activation of NF-κB pathway in the small pulmonary artery endothelial cells,attenuate the pulmonary vascular inflammation and prevent the MCT-induced pulmonary hypertension in rats.

Background Acute lymphoblastic leukemia (ALL) and chemotherapy can cause immune imbalance,and gaseous molecule hydrogen sulfide (H2S) can participate in the process of immune response.This study aimed to investigate the immune regulation of H2S in pediatric ALL.Methods Children (n=78) with ALL admitted during 2010-2013 were included in this study.Two blood samples were collected in period of before chemotherapy,bone marrow remission and two days after chemotherapy,respectively.Serum contents of H2S and cytokines,including interleukin-1β (IL-13),interleukin-2 (IL-2),interferon-γ (IFN-γ),tumor necrosis factor (TNF-α),interleukin-4 (IL-4),interleukin-6 (IL-6),interleukin-10 (IL-10) and macrophage inflammatory protein-1α (MIP-1a),were detected using ELISA method.Stepwise regression was used to analyze the correlation between H2S and cytokines.Furthermore,human Jurkat cells were cultured in vitro,and nucleoprotein of Jurkat cells and peripheral blood mononuclear cells (PBMCs) were collected,contents of cystathionine γ-lyase (CSE) and certain cytokines were measured by Western blotting.Results Serum concentrations of H2S,IL-13,IL-6,IL-10 and MIP-1α in children with ALL were increased significantly (P ＜0.01),while concentrations of IL-2,TNF-α,IFN-γ and IL-4 decreased obviously (P ＜0.01).In patients after chemotherapy,concentrations of H2S and IL-10 were decreased significantly (P ＜0.05),but IL-4 and IFN-γ concentrations increased markedly (P ＜0.05).At remission stage,H2S,IL-13,IL-4,IL-6,IL-10 and MIP-1α concentrations were further decreased markedly (P ＜0.05),but concentrations of IL-2,TNF-α and IFN-γ increased again (P ＜0.05).Protein contents of CSE,IL-10,IL-4 and IL-2 of PBMCs also increased markedly in children with ALL.Moreover,changes of CSE protein contents of PBMCs were consistent with serum H2S contents,and there were significant correlation between H2S and certain cytokines based on stepwise regression analysis.Furthermore,compared with those of PBMCs group,in vitro study indicated that Jurkat cells of H2S group expressed IFN-γ,IL-10,IL-4 and IL-2 protein increased obviously (P ＜0.05),while IL-4,IL-2 and CSE expression of PPG group decreased markedly (P ＜0.05).Conclusion Gaseous molecule H2S might participate in the process of immune regulation in pediatric ALL through modulating transcription and expression of cytokines.

Background Bacterial inflammation is a common complication in patients with leukemia,and sulfur dioxide (SO2) is a bioactive molecule in modulating Gram-negative bacilli infection.This study aimed to examine the changes in SO2,nuclear factor-κB (NF-κB),and interleukin-8 (IL-8) levels in pediatric acute lymphoblastic leukemia (ALL) with Gram-negative bacterial inflammation.Methods Fifty-five ALL children were enrolled in this study,including 30 males and 25 females,aged 3-13 years,and the median age was 7.8 years.All these children who accepted chemotherapy for ALL were divided into the control group (before chemotherapy),the infection group (after chemotherapy with infection),and the recovery group (the infection was controlled after 1 week).The serum level of SO2 was detected using high performance liquid chromatography with fluorescence assay,and NF-κB and IL-8 levels were measured by enzyme-linked immunosorbent assay (ELISA).Human THP-1 cells were cultured,induced,and differentiated into macrophages,which were divided into five groups and each group was cultured with different stimulators:lipopolysaccharide (LPS) group,LPS+L-aspartate-β-hydroxamate (HDX) group,LPS+SO2 group,SO2,and control groups.NF-κB level and IL-8 protein contents by ELISA were examined in each group.Results In comparison with those of the control group,levels of serum SO2,NF-κB,and IL-8 of the infection group were significantly increased (P ＜0.05),while those of the recovery group were significantly decreased (P ＜0.05).A positive correlation was found between levels of serum SO2 and intracellular NF-κB/IL-8,and the correlation coefficients were 0.671 and 0.798 (P ＜0.05),respectively.According to the results found in human THP-1 cells,levels of NF-κB and IL-8 in LPS group were significantly increased compared with those of the control group (P ＜0.05); when compared with those in LPS group,levels of NF-κB in LPS+HDX group further increased significantly (P ＜0.05); however,the NF-κB levels of LPS+SO2 group decreased significantly (P ＜0.05).Conclusion SO2 may play an anti-inflammatory role during the process of inflammation by inhibiting the activation and transcription of NF-κB.