ABSTRACT
The atmospheric particulate matter(PM) is widely regarded as one of major environmentally and unfriendly ambient air pollution, and therein PM2.5 (diameter≤2.5 μm) is most closely related to human health.Because of its smaller diameter with longer suspension duration, PM can absorb many pathogenic microorganisms, and easily enter into the deep of airway and then deposit on the bronchus and alveoli, and it brings damage to the lung tissues and the surfactant proteins.PM can give rise to oxidative stress, inflammation response, cells and DNA damage.Now, this review focuses on the characterization and composition of PM, as well as the impact of PM2.5 on the lung, surfactant proteins and human health, which helps to call for more people to pay attention to this environmental issue in order to better mitigate and prevent the damage caused by PM.
ABSTRACT
The atmospheric particulate matter(PM) is widely regarded as one of major environmentally and unfriendly ambient air pollution,and therein PM2.5 (diameter≤2.5 μm) is most closely related to human health.Because of its smaller diameter with longer suspension duration,PM can absorb many pathogenic microorganisms,and easily enter into the deep of airway and then deposit on the bronchus and alveoli,and it brings damage to the lung tissues and the surfactant proteins.PM can give rise to oxidative stress,inflammation response,cells and DNA damage.Now,this review focuses on the characterization and composition of PM,as well as the impact of PM2.5 on the lung,surfactant proteins and human health,which helps to call for more people to pay attention to this environmental issue in order to better mitigate and prevent the damage caused by PM.
ABSTRACT
Objective To evaluate the effects of PM2.5 on the differentiation of splenic CD4 + T lymphocytes in acute asthma mice.Methods (1) Mouse models of acute asthma were established by ovalbumin (OVA) sensitization and challenge.(2) PM2.5 was collected in the urban area of Zhanjiang city under heavy traffic and serious air pollution from total suspended particulate(TSP) mid-flow sampler and multistage particles cutters and the dry powder of PM2.5 was prepared.(3) Specific-pathogen free Balb/c mice,female,at 6 to 8 weeks of age were randomly divided into 8 groups (8 mice each group):a negative control group (NC group),asthma control group (AC group),sensitized mice treated with different doses of PM2.5 groups (SP groups) and asthmatic mice treated with different doses of PM2.5 groups (AP groups).SP groups and AP groups were respectively divided into 3 subgroups according to the dose of PM2.5.The AC group,SP groups and AP groups were sensitized on D0,D7 and D14,and the NC group was treated with NS as controls.The SP1/AP1 group,SP2/AP2 group and SP3/AP3 group were respectively given 50 μL PM2.5 suspension.NC group and AC group were instilled with NS as controls.AC group and AP groups were challenged by aerosol of OVA,and NC group and SP group were treated with NS as controls.Twenty-four hours after last challenge,all the mice were sacrificed,and the percentage of regulatory T cells (Treg),T helper cell type 1 (Th1),Th2 and Th17 of splenic CD4 + T lymphocytes was detected by flow cytometry (FCM).Results (1) An OVA-induced mouse models with acute asthma were successfully established.(2) Comparison of the percentage of Treg of splenic CD4 + T lymphocytes:SP group [(12.28 ± 0.73) ％,(11.93 ± 0.81) ％ and (11.70-± 1.14) ％] and AC group [(12.18 ± 1.00) ％] were lower than that in the NC group[(13.50 ± 0.39) ％] (P ＜ 0.05),AP3 group [(10.58 ± 0.65) ％] was lower than that in the AC group and AP1 group [(11.91 ± 0.79) ％] (P ＜ 0.05).(3) Comparison of the ratio of Th1/Th2 of splenic CD4+ T lymphocyte:SP1 group [(7.74 ± 1.21)％] was higher than that in the NC group [(5.52 ± 1.06) ％] (P ＜0.05),SP2 group[(6.30 ±0.58) ％] was lower than that in the SP1 group(P ＜0.05),SP3 group [(4.87 ± 0.82) ％] was lower than that in the SP2 group (P ＜ 0.05);AC group [(3.69-± 0.47) ％] was lower than that in the NC group and SP3 group (P ＜ 0.05);AP3 group [(2.92 ± 0.57) ％] was lower than that in the AC group(P ＜ 0.05).(4) Comparison of the percentage of Th17 of splenic CD4+ T lymphocyte:AP3 group [(1.46 ± 0.39) ％] was higher than that in the NC group [(0.89 ± 0.24) ％] and the AP2 group [(0.83 ± 0.15) ％] (P ＜ 0.001).Conclusions PM2.5 can inhibit splenic CD4 + T lymphocyte of acute asthma mice differentiation into Treg and Th1,and promote their differentiation into Th2 and Th17,through which aggravates inflammation reactions in the airway.
ABSTRACT
Objective To explore the effects of combining tumor necrosis factor-α (TNF-αt) inhibitor with adenosine A2b receptor antagonist CVT-6883 on asthmatic lung irflammation in mice.Methods A total of 40 female Balb/c mice were evenly randomized into 5 groups,including normal control group,asthma group,CVT-6883 group,CVT-6883 + etanercept group,and etanercept group.The pathological changes in the lungs were determined and the number of white blood cells(WBC) and eosinophil(EOS) in the bronchoalveolar lavage fluid(BALF) was counted by cell count in each group.The levels of TNF-α in BALF were evaluated by enzyme-linked immunosorbent assay (ELISA).The expression of adenosine A2b receptor mRNA in the lung tissues were measured by reverse transcriptionpolymerase chain reaction (RT-PCR).Results 1.The lung tissue in asthma group,dyed by HE,was found to have a large number of airway inflammatory cell infiltration,thickening of the bronchial mucosa,the alveolar septa widened and fracture.In the CVT-6883,CVT-6883 + etanercept and etanercept group,the pathological changes were relieved.2.The WBC and EOS counts in BALF of the asthma group[(413.8 ±5.8)/L,(139.3 ± 1.4)/L] were higher than those of the normal control group [(24.0 ± 1.3)/L,(1.8 ± 0.1)/L,P ＜ 0.05].The WBC and EOS counts of the CVT-6883 group[(111.5 ±3.8)/L,(3.3 ±0.1)/L],the etanercept group + the CVT-6883 group[(173.8 ±3.9)/L,(10.4 ± 0.2)/L],and the etanercept group[(138.4 ± 3.0)/L,(4.1 ± 0.1)/L] were lower than those of the asthma group (P ＜0.05).3.Compared with the control group(100.4 ± 5.7) ng/L,the TNF-α concentration of the asthma group (145.2 ± 8.8) ng/L was significantly higher (P ＜ 0.05) ; the TNF-α concentration of CVT-6883 group (130.9 ± 5.9) ng/L,CVT-6883 + etanercept group(115.7 ± 8.2) ng/L and the etanercept group(122.0 ± 8.7) ng/L,were significantly decreased compared with asthma group (P ＜ 0.05).4.In asthma group (8.9 ± 1.1) compared with the control group(0.6 ± 0.2),the A2bAR (adenosine A2b receptor) mRNA expression was upregulated (P ＜ 0.05) ; CVT-6883 group(1.6 ±0,3),CVT-6883 + etanercept group(2.5 ±0.6) and the etanercept group(5.3 ±0.4),the A2bAR(adenosine A2b receptor) mRNA expression was significantly decreased compared with asthma group (all P ＜0,05).Conclusion Combination of TNF-α inhibitor with adenosine A2b receptor antagonist can reduce asthmatic lung inflammation.
ABSTRACT
Objective To investigate the effect of different adjuvants and challengemethods on asthma mice′s lung inflammation . Methods BALB/c mice were sensitized with ovalbumin in aluminium hydroxide or alum adjuvant .After 7 days challenges ,choose the proper adjuvant with intranasal or atomized to prepare mice asthma model .Count and classify the white blood cells (WBC) in bronchoalveolar lavage fluid(BALF) ,observe the peribronchial and perivascular inflammation .Results Compare the WBC and eos-nophils in BALF ,the alum group are higher than aluminum hydroxide group(P0 .05) .10 days after the last challenge ,the inflammation fade sharply ,and the corresponding result occured in the lung inflammation .Conclusion In establishing asthma model ,alum is better than aluminum hydroxide ,atomization is better than intranasal .Inflammation will fade after stop atomization a period of time .
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of adenosine and its agonist on hypoxia-induced right ventricular hypertrophy (RVH) and explore the underlying mechanism.</p><p><b>METHODS</b>Fifty-six rats were randomly divided into normoxia group, hypoxia group, and treated hypoxia groups (with different treatments with adenosine, A1 receptor agonist CPA, A2 receptor agonist NECA, CPA plus A1 receptor inhibitor DPCPX, or NECA plus A2B receptor inhibitor MRS1754). The rats except for those in normoxia group were exposed to normobaric chronic hypoxia (9.5%-10.5% oxygen) for 21 days, and the corresponding treatments were administered since the 7th day of hypoxia till day 21 via implantable capsule with a pressure pump. After the treatments, the right ventricles were then removed and weighed for evaluation of hypertrophy, and the expressions of NHE-1 and CnAβ mRNA in the myocardial tissue were detected using RT-PCR.</p><p><b>RESULTS</b>After a 21-day hypoxia, the rats showed significantly increased RV/(LV+S) ratio (0.369∓0.033) and RV/BW ratio (0.75∓0.095) compared to those in normoxia group (0.271∓0.010 and 0.59∓0.039, respectively; P<0.001), adenosine treatment group (0.281∓0.022 and 0.65∓0.077, respectively; P<0.001, P=0.025), hypoxia with CPA group (0.313∓0.021 and 0.66∓0.067, respectively P<0.001), and hypoxia with NECA group(0.333∓0.019, and 0.68∓0.074, respectively P<0.001). The NHE-1 and CnAβ mRNA levels in hypoxia group were significantly higher than those in normoxia group, adenosine treatment group, hypoxia with CPA group, and hypoxia with NECA group(P<0.001).</p><p><b>CONCLUSION</b>Adenosine and its agonist can inhibit hypoxia-induced RVH in rats through the NHE-1/CaN signal pathway.</p>
Subject(s)
Animals , Male , Rats , Adenosine , Pharmacology , Hypertrophy, Right Ventricular , Metabolism , Hypoxia , Metabolism , Rats, Sprague-Dawley , Signal Transduction , Sodium-Hydrogen Exchangers , MetabolismABSTRACT
Background: Epigenetic mechanisms of gene transcription, including inactivation of tumor suppressor genes by hypermethylation and activation of oncogenes by hypomethylation, have been shown to contribute to breast tumorigenesis. Phosphatase and tensin homolog deleted on chromosome ten (PTEN) and Spleen tyrosine kinase (SYK) are both tumor suppressor genes and survivin is a novel member of the inhibitor of apoptosis (IAP) family which may promote tumorigenesis.Objective: To investigate the methylation status of PTEN, SYK, and survivin genes in breast cancer derived from Chinese women.Materials and methods: We examined the methylation status of these three genes in 52 paraffin-embedded breast cancer tissues using methylation-specific PCR (MSP) assay in conjunction with sequencing analysis.Results: PTEN and SYK were both methylated in 15.4% (8/52) of breast tumor tissues, while the survivin gene was all demethylated in the examined samples. Random selection of MSP products sequence analyses to three genes all revealed a homogenous methylation status in the CpG sites.Conclusion: The present study showed a moderate methylation status of PTEN and SYK, and an unmethylation status of survivin in breast tumor tissues derived from Chinese women, which suggested methylation mechanisms might be involved in the aberrant expression of these three genes in breast cancer development.
ABSTRACT
Objective Many studies showed that Ca~(2+) channel blocker could prevent and treat right ventricular hypertrophy(RVH) induced by chronic hypoxia.To further identify the mechanism,we investigated the effect of Ca~(2+) channel blocker on the levels of myocardial calcineurin A?mRNA(CnA?)in RV and plasma nitric oxide(NO),NO synthase and endothelin-1(ET-1) in rats with chronic hypoxia.Methods 30 rats were divided into three groups by randomized block design: treatment group with Amlodipine Besylate ablets [(30 mg?kg~(-1)?d~(-1)),administered via gavage],chronic hypoxia group,and control group.The rats in treatment group and chronic hypoxia group were exposed to normobaric chronic hypoxia [(10.0?0.5)% O_2 ] for 21 days.On the 21st day of experiment,all rats were sacrificed and the hearts were collected for measuring the weight.Blood samples were also drawn from the ventricles for measuring plasma NO,iNOS and ET-1 levels.CnA?mRNA levels in RV were measured by RT-PCR.Results ⑴The RV/(LV+S)、RV/BW ratios were significantly higher in chronic hypoxia group than those of control group and treatment group(P
ABSTRACT
Objective To explore the effect of calcium gene-related peptide (CGRP) on free calcium concentration in the brain cells of hypoxic-ischemic neonatal SD rats. Methods Animal model of hypoxic-ischemic cerebral injury was set up using SD rats of 7 days old. Then the rats were randomly divided into treatment group given 3?g/kg/d CGRP intraperitoneally for 3 days immediately after the model was made, and salt solution group given 0.9% NaCl solution intraperitoneally for 3 days. Normal control group received sham operation. All the rats were decapitated after 3 days and the concentration of free calcium in brain cells was measured with calcium fluorescence indicator in Fura-2Am. Results The free calcium concentration in brain cells in salt solution group was significantly higher than that in the other two groups (P
ABSTRACT
AIM: To observe the expression of TNF-?, I L-6 mRNA in injured myocardium caused by infectious pneumonia and the effects of exogenous adenosine.METHODS: Fifty rats were divided into five experimental groups at random. The model of pneumonia was replicated by the inj ection of staphylococcus aureus into the windpipe of rats. Adenosine-treated ra ts (A,B and C group) received daily injection of adenosine at different dosages (50, 100 and 150 ?g?kg -1 ?min -1 for 90 min) for 3 days. All rat s were killed on the fifth day. Pathological examination of myocardium were don e and TNF-?, IL-6 mRNA expression were detected by reverse transcription poly m erase chain reaction (RT-PCR). RESULTS: (1) Significant increa se in TNF-?, IL-6 mRNA expression was observed in myocardium of pneumonic rats compared with control group ( P0 05). IL-6 mRNA expression in adenosine-treated C group was lower than that in adenosine-treated B group ( P
ABSTRACT
AIM: To study the role of calcineurin in the progression of right ventricle cardiac hypertrophy in the chronic hypoxia rats and examine the effect of Ca 2+ channel blockers on the activation of calcineurin. METHODS: Sixty rats were divided into three groups: treatment group with amlodipine besylate ablets, chronic hypoxia group, normal control group with normal oxygen. The rats in treatment group and chronic hypoxia group were exposed to normobaric chronic hypoxia(10?0 5)% O 2 for 21 days. All hearts were removed immediately after dissection for further investigation. RESULTS: (1)The RV/(LV+S),RV/BW were significantly higher in hypoxia group than that of control group and treatment group( P
ABSTRACT
Objective To observe the effect of PM2.5 on the secretion of NO, ET-1 and the proliferation of rat vascular smooth muscle cell(VSMC) in vitro.Methods VSMCs were treated with PM2.5 collected from urban area of Zhanjiang,at the doses of 10,20,50,100 and 200 ?g/ml.After 24 hours of treatment, the levels of NO and ET-1 in the VSMCs were detected by nitrate reductase method and radioimmunoassay respectively, the proliferation of VSMCs was detected by MTT.Results At the concentrations of 10-200 ?g/ml, with PM2.5 increased, the level of NO in VSMCs decreased from(43.53 ?3.46)?mol/L to(29.28?2.28)?mol/L(F=18.89,P
ABSTRACT
Objective To investigate the clinical features of Henoch-Schonlein purpura nephritis(HSPN) and the clinical significance of plasma endothelin-1(ET-1) in HSPN.Methods The epidemiology and clinical characteristics were retrospectively analyzed in 84 patients admitted to our hospital from January 2000 to March 2005.The changes of ET-1 were measured in 84 patients and 16 controls by using radioimmunologic assay.Results The age of onset in HSPN was 5-10 years and the corresponding patients occupied 90.6%.The majority of HSPN cases(80.32%) occurred from September to March of the second year.Infection was still the main occasion factor(40.57%),and the mistaken diagnosis at rate of 33.33% as acute gastricism and appendicitis when gastrointestinal sign appeared earlier than the typical purpura.The nephritic syndrome was the most constant clinical manifestation(47.63%).The pathological type of grade Ⅱ was 37.84%,grade Ⅲ 56.40%.The level of plasma ET-1 in patients was more higher than that of normal controls.The level of plasma ET-1 had a positive correlation with plasma urea nitrogen and creatinine(r=0.584,0.523,P
ABSTRACT
AIM: To study the protective effects of intravenous (iv) CGRP on myocardial injury in rat. METHODS: Establish a rat myocardial ischemic injury model by subcutaneous injection of single dose of isoproterenol (ISO), and treat the model with single dose of iv CGRP. Two hours later, serum CK, LDH, MDA and SOD levels were measured, MDA and SOD in myocardial tissue were tested, and myocardial tissue structures were observed. RESULTS:(1) Serum MDA and tissue MDA levels increased significantly and serum SOD and tissue SOD decreased significantly in injury group, in the CGRP treated group, the above changes were reversed (P
ABSTRACT
AIM: We used an animal model of chronic hypoxia to mimic right ventricular hypertrophy and try to study the potential mechanism of myocardium apoptosis of right heart in rat under chronic hypoxia.METHODS: Rat hypoxia models were established by exposing the rats to normobaric chronic hypoxia(oxygen levels were maintained at 9.5%-10.5%).Sixty rats were separated into two groups: one exposed to hypoxia and the other serving as control.Ten rats,randomly selected from each group were killed at 14,21,28 d after hypoxia.The apoptosis was determined.The changes of RV weight to left ventricle and interventricular septum weight ratio[RV/(LV+S)],the RV weight to body weight ratio(RV/BW) were also observed.The ?-MHC,bcl-2 and bad mRNA levels in right ventricle were detected by semi-quantitative RT-PCR assays and expression of ?-MHC,Bcl-2 and Bad protein levels were detected by Western blotting.RESULTS: The RV/(LV+S),RV/BW and apoptosis index in chronic hypoxia group were higher than those in normal control group(P0.05).Finally,a decreased bcl-2/bad ratio in chronic hypoxia group was found compared with control group(P