OBJECTIVE To investigate the genome protective effects of anti-malaria drug,artesunate in an experimental allergic asthma model.METHODS Mice were sensitized on day 0 and 7 and challenged on day 14 with 100μg house du...OBJECTIVE To investigate the genome protective effects of anti-malaria drug,artesunate in an experimental allergic asthma model.METHODS Mice were sensitized on day 0 and 7 and challenged on day 14 with 100μg house dust mite(HDM)via intratracheal administration.Artesunate(30mg·kg-1)was administered intra-peritoneally on day 6,7,8,13,14 and 15.Samples were collected on day 1,3 and 5 post last HDM-challenge for analysis of air way inflammation and DNA damage.Lung sections were immunofluorescence(IF)-stained for DNA double strand breaks(DSBs)markers,γH2AX and 53BP1.Levels of DNA repair proteins Ku70 and Rad51,which are involved in non-homologous end joining(NHEJ)and homologous recombination(HR)DNA DSB repair pathways respectively,were measured.To quantify cell death in asthmatic lung,TUNEL staining was performed.Comet assay,a single cell gel electrophoresis was employed to detect DNA damage induced by HDM in BEAS-2Bhuman bronchial epithelial cell line,in vitro.RESULTS Artesunate treatment significantly reduces immune cells infiltration in BAL fluid of asthmatic mice,collected on day 3 and 5 post-challenge.Importantly,artesuante is able to protect bronchial epithelium from DNA DSBs induced by asthma,as detected by the reduced level of γH2AX and 53BP1 foci formation in the nucleus.This genome protective effect is evident even on day 1 post-challenge,when immune cells infiltration remained high.This indicates that artesunate confers protection on bronchial epithelium in the presence of inflammation.Additionally,artesunate is also able to reduce cell death in asthmatic lung revealed by TUNEL assay and cleaved caspase 3 level.Interestingly,the levels of DNA repair proteins in artesuante-treated asthmatic mice are unchanged as compared to HDM-only mice,suggesting that artesunate treatment does not augment the level of DNA repair proteins.When human bronchial epithelial BEAS-2 Bcells were exposed to HDMin vitro,we observed an increase in the levels of DNA damage.Artesunate(60μmol·L-1)co-incubated with HDM is not able to prevent direct DNA damage induced by the allergen.Together,these studies suggest that the genome protective effect of artesunate in vivo may be attributed to physiological effects(such as its anti-inflammatory effects)rather than serving to directly prevent DNA damage.CONCULSION This study highlights a novel role for artesunate in protecting bronchial epithelial cells from asthma-induced DNA damage.展开更多
Epidemiological studies have shown that there is a link between asthma and brain damage,but toxicological studies have not fully confirmed yet,especially the effects of asthma on the brain. In this study,at first,we e...Epidemiological studies have shown that there is a link between asthma and brain damage,but toxicological studies have not fully confirmed yet,especially the effects of asthma on the brain. In this study,at first,we explore the effects of asthma on the brain through the establishment of an allergic asthma model. Then PM_(2.5),a typical outdoor air pollutant and formaldehyde,a typical indoor air pollutant were selected to be closer to the true environment and find whether there is any synergism between them. In this study,an ovalbumin( OVA)-sensitized mice asthma model was established. 30 male Balb/c mice were randomly divided into 5 groups:( 1) saline control group,( 2) OVA-sensitized group,( 3) OVA-combined with formaldehyde exposure group,( 4) OVA-combined with PM_(2.5) exposure group,( 5) Combination of OVA,formaldehyde and PM_(2.5) exposure group. The mice were inhaled with formaldehyde or/and instilled with PM_(2.5) from day 1 to 18. The mice asthma model was developed by OVA sensitization and challenge. The mice were sensitized with OVA+Al( OH)3( 5 mg OVA and 175 mg Al( OH)3 in 30 m L saline each time) or saline( 30 m L saline each time) by intraperitoneal injection on day 1,7 and 14.This was then followed by an aerosol challenge in 1% OVA( 30 min·d^(-1)) from day 19 to 25( 7 times) using an ultrasonic nebulizer. On the 26 th day,the organ coefficient of mice brain was counted,then the contents of oxidative stress of mice brain were measured,including reactive oxygen species( ROS),glutathione( GSH) and malondialdehyde( MDA),and the concentrations of NF-κB and interleukin-1β( IL-1β) were detected by using ELISA kits.Detection of interleukin-6( IL-6) was made with immunohistochemical method. Histological assay for brain was also conducted. In our results,all the OVA treated groups showed a significant increase of ROS and a significant decrease of GSH contents when compared with the control group. Except OVA-sensitized group,other OVA treated groups also showed a significant increase of MDA contents when compared with the control group,and MDA contents of OVA-sensitized group showed significant change when compared to the combined exposure group. In ROS and GSH,combined exposure showed some joint effect compared with single exposure. When OVA was applied in combination with formaldehyde and PM_(2.5),NF-κB was activated. And all the OVA treated groups showed increased levels of IL-1β and IL-6 compared with the control group. And the combined exposure showed an aggravated effect when compared with OVA-sensitized group. Histopathological observation of the hippocampus in mice brain clearly showed the difference of eosin( EO) stained neurons in the combined exposure group compared with the control group and OVA-sensitized group. The pyramidal neurons of the mice with allergic asthma exposed to formaldehyde and/or PM_(2.5) had been reduced in number,the cells were swollen and the dendrites had disappeared. Allergic asthma can cause damage to the brain through oxidative stress. Exposure to formaldehyde and PM_(2.5) will increase the damage caused by allergic asthma to the brain,which may be mediated by oxidative stress and NF-κB activation.This promotes the release of the inflammatory factors,resulting in increased inflammation.展开更多
OBJECTIVE The study aims to evaluate intranasal(i.n.)curcumin at 5mg·kg-1,its absorption through nasal mucosa reaching blood and lungs and investigate its anti-allergic and anti-asthmatic potentiality in ameliora...OBJECTIVE The study aims to evaluate intranasal(i.n.)curcumin at 5mg·kg-1,its absorption through nasal mucosa reaching blood and lungs and investigate its anti-allergic and anti-asthmatic potentiality in ameliorating ovalbumin induced asthma in mouse model.METHODS A simple and sensitive high performance liquid chromatography method using UV detection(HPLC-UV)was developed and validated for the determination of nasal curcumin 5mg·kg-1 in nasal mucosa,plasma and lungs from 15min-6hof post dosing and further applied to determine the pharmacokinetics parameter.Further,for the anti-asthmatic study,BALB/c mice were sensitized(day 1,7and 14)and challenged with ovalbumin(day 19-22)and treated with intranasal curcumin 5mg·kg-1(in the form of nasal drops)before an hour of challenge(day 19-22)to investigate its therapeutic effect on various parameters of airway inflammation as detected in the bronchoalveolar lavage fluid,serum and lung tissue.Serum was also used to study the liver kidney function test for the toxicity.RESULTS The validated method of HPLC was sensitive with a lower limit of quantitation of 5μg·mL-1 and the calibration curve represented good linearity(r2≥0.999)over the linear range of 5-50μg·mL-1.HPLC study reveals,absorption and quantification of curcumin as 1.9μg·mL-1 in the nasal mucosal scrapping at 15 min elevating to 4.9μg·mL-1 till 1h and declining to 3.2μg·mL-1 till 3h after intranasal administration of curcumin(5mg·kg-1).The plasma showed 0.9μg·mL-1 after 15 min spiking upto 1.5μg·mL-1 till 3h while lung homogenate retained up to 3.6μg·mL-1 of curcumin till 3h,which was detectable from 15min(0.27μg·mL-1)and was on higher side as compared to earlier studies.The same pharmacological dose(5mg·kg-1,i.n.)has shown anti-asthmatic potential by inhibiting airway inflammation(eosinophilic inflammation),bronchoconstriction and modulation in cytokines level of Th2(IL-4,IL-5),Th1(IFN-γ)and proinflammatory(TNF-α)cytokines in ovalbumin induced asthma without having any side effect as detected by liver kidney function test.CONCLUSION The study reveals nasal mucosa as a viable route for the absorption of intranasal curcumin and accommodating increased transportation to the blood and lungs.Also,the nasal route is effective in retaining the level of curcumin till 6h without any degradation and hence could be a promising route to improve its biological activities.Present study may prove the possibility of curcumin as complementary medication in the development of nasal drops or through nebulizer in human subjects.Further,pharmacodynamic study is in progress to prove its effectiveness not only in pulmonary disorders but also for systemic disorders.展开更多
OBJECTIVE Airway wall remodeling(AWR),which refers to structural changes in the airway,is a key characteristic of asthma.Airway smooth muscle(ASM)cell hypertrophy and hyperplasia contributes to AWR.Glucocorticoids,whi...OBJECTIVE Airway wall remodeling(AWR),which refers to structural changes in the airway,is a key characteristic of asthma.Airway smooth muscle(ASM)cell hypertrophy and hyperplasia contributes to AWR.Glucocorticoids,which are used as first line therapy for the treatment of asthma,reduce ASM proliferation but the magnitude of their anti-proliferative actions is dependent on the mitogen used.Moreover,glucocorticoid therapy is accompanied by many side effects.Artesunate,a semi-synthetic artemisinin derivative,has been widely used to treat malaria with minimal toxicity.Artesunate has been shown to attenuate allergic airway inflammation in mice.However,its role in treating AWR in asthma is not known.In this study,we hypothesize that artesunate has anti-proliferative actions on ASM cells,potentially reversing AWR.METHODS and RESULTS Quiescent primary human ASM cells were pre-treated(1h)with artesunate(3,10,30μmol·L-1)before being stimulated with either FBS(10%)or thrombin(0.3U·mL-1).Following 48 h stimulation with mitogen,cells were counted using a haemocytometer.Dexamethasone(Dex,100nmol·L-1)was used as a positive control.Artesunate concentration-dependently reduced cell number and the magnitude of inhibition appeared to be non-mitogen dependent.Moreover,we examined the effect of artesunate on two important signalling proteins involved in cell proliferation,ERK1/2phosphorylation and cyclin D1 protein levels.Artesunate reduced cyclin D1 protein levels significantly following 20 h stimulation with either thrombin or FBS but had no effect on ERK1/2 phosphorylation following 6h stimulation.Importantly,artesunate(30μmol·L-1),but not Dex,inhibited the phosphorylation of Akt,which is upstream of cyclin D1.Next,we show that the inhibitory effect of artesunate,but not Dex,on ASM cell number is retained at least 24h post-treatment following stimulation with FBS.In an acute murine model of allergic asthma,artesunate treatment decreased sm-α-actin positive cells and cyclin D1 protein abundance in the ovalbumin sensitized and challenged mice.CONCLUSION We have shown that artesunate regulates the PI3K/Akt pathway to inhibit the proliferation of primary human cultured ASM cells.This is an alternative mode of action,in comparison to glucocorticoids such as Dex.The anti-proliferative effect of artesunate was further validated in vivo.Thus,our study provides a basis for the future development of artesunate as a novel anti-AWR agent that targets ASM hyperplasia via the PI3K/Akt pathway.Moreover,artesunate may be used as an add-on therapy for asthmatic patients.展开更多
Targeted peptides have been identified as showing great promise for treatment of various diseases including asthma.Asthma is considered of difficuIt-to-treat due to its unclear etiology,thus usually requiring life-lon...Targeted peptides have been identified as showing great promise for treatment of various diseases including asthma.Asthma is considered of difficuIt-to-treat due to its unclear etiology,thus usually requiring life-long treatment.Current strategies for asthma therapy are hampered with undesirable side effects,poor targeting and failure in modulating airway hyperresponsiveness,leading to pressing need of developing more targeted and effective therapeutic sites for asthma.Recently,a disintegrin and metalloproteinase 8(ADAM8)have been shown to over-展开更多
Introduction Excessive narrowing of airways is the most important pathological feature of asthma,but its mechanism remains puzzling.One certain thing is that the contraction of airway smooth muscle(ASM)ultimately caus...Introduction Excessive narrowing of airways is the most important pathological feature of asthma,but its mechanism remains puzzling.One certain thing is that the contraction of airway smooth muscle(ASM)ultimately causes airway narrowing,thus both structural and functional alterations of airway smooth muscle(ASM)are thought as common final pathway responsible for the bronchial hyperresponsiveness(BHR),the hall mark of asthma.Many chemical and physical factors such as air pollutants,inflammatory agents,mechanical and geometrical properties of the microenvironment could influence structure and/or function of ASM cells.In addition,some re-展开更多
Prevention and treatment of 88 cases of asthma with acupoint application therapy.Analyses of the mechanism of treatment according to the Traditional Chinese Medicine(TCM)theory and laboratory test results.
Objective:To assess the haematological and lipid profile assays in asthmatics.Methods: Eighty asthmatic subjects were prospectively studied in a major referral centre serving the Niger Delta region of Nigeria for 12 m...Objective:To assess the haematological and lipid profile assays in asthmatics.Methods: Eighty asthmatic subjects were prospectively studied in a major referral centre serving the Niger Delta region of Nigeria for 12 months(2006-2007).Clinico-haematological and serum lipid total cholesterol(TC),triglyceride(TG),and lipoproteins concentration were analyzed after adjusting for age,cigarette smoking,alcohol ingestion,hypertension and diabetes mellitus.Results: Eighty patients(34 males and 46 females) were seen with female predominating in the various age groups(M∶F ratio,0.7∶1).Total cholesterol and low density lipoproteins-cholesterol for the asthmatics was significantly higher than the controls(P<0.000 1),while the ratio of TC∶HDL-C(high density lipoprotein-cholesterol) in asthmatics was 3.67 compared to the control value of 3.01.TC and low density lipoprotein-cholesterole(LDL-C) were significantly higher in females than the males(P<0.05).There was a combined hypertriglyceridemia(HT,>2.3mmol/L) and a significant hypercholesterolemia(HC,>5.2mmol/L) according to the Adult Treatment Panel III definition in asthmatics thereby putting them at increased risk for the development of cardiovascular disease as well as other disorders related to excess lipids.There was a significant thrombocytopenia(P<0.000 1) which may accompany allergen exposure and this persists for 24 h;that asthmatics of African descent showed a significantly increased total leucocyte count(P=0.001) similar to other studies in the Western countries.Conclusion: Hyperlipidaemia is a prevalent medical problem among asthmatics;hence screening for fasting serum lipid levels to identify those who need early intervention is recommended.展开更多
Objective: The aim of this study was to assess school indoor exposure to microbial products and prevalence of asthma and allergies in rural and urban children.Methods: This study was carried on a rural and an urban sc...Objective: The aim of this study was to assess school indoor exposure to microbial products and prevalence of asthma and allergies in rural and urban children.Methods: This study was carried on a rural and an urban school.Environmental endotoxin level was measured in multiple samples of the ambient indoor air dust collected on special aseptic filter papers from the two schools.For two hundred children history taking,clinical examination,allergen skin prick test and basic pulmonary function test were preformed.Results: Environmental endotoxin levels showed significantly higher mean values(P<0.01) in rural school(3 EU/mg) as compared to the urban school(0.1 EU/mg) with(OR=5.163;95% CI: 0.95-28).History of allergic symptoms was significantly more in urban than rural students(P=0.01).Mean values of pulmonary function parameters were significantly lower values in urban students compared to rural students.Skin prick test results showed significant reactions to all tested allergens in urban children compared to rural children(P<0.05).Conclusion: There is an inverse association between environmental exposure to endotoxins and susceptibility for allergic manifestations in school children.展开更多
OBJECTIVE Using bronchial asthma rats,to observe the effects of Smooth wheezing effect of polysaccharide.In addition,to study the effects of COM in different bronchial asthma model.METHODS Bronchial rats established b...OBJECTIVE Using bronchial asthma rats,to observe the effects of Smooth wheezing effect of polysaccharide.In addition,to study the effects of COM in different bronchial asthma model.METHODS Bronchial rats established by ovalbumin(OVA),were randomly divided into different group.Every other week building reference literature intraperitoneal injection of OVA,21 d after injection of 3 consecutive ultrasonic atomization inhalation of 1% OVA stimulating 30 d,stimulate the 31 d began to medicine.Lavage for 4 weeks ELISA test ratio of IgE,SP-A,IL-4 and IL-5 was serum and bronchoal veolar lavage fluid etc.Data was in x±s tabular format,SPSS16.0 statistics software is used to perform statistical analysis on the data,and P<0.05 shows meaningful statistical difference.RESULTS Quince polysac.charide can reduce the IgE,IL-4 level and elevated the SP-A,IL-5 level in serum and bronchoal veolar lavage fluid.CONCLUSION Quince polysaccharide has antiasthmatic effect on bronchial asthma rats.展开更多
Objective:Asthma can be a disabling disease and despite advances in pharmacology,the prevalence of this condition globally remains high and accounts for a significant proportion of public health care costs.While pharm...Objective:Asthma can be a disabling disease and despite advances in pharmacology,the prevalence of this condition globally remains high and accounts for a significant proportion of public health care costs.While pharmacology is the mainstay of asthma management,drug side effects have promoted alternative therapeutic interventions,such as acupuncture.Acupuncture points have a lower skin impedance compared to non-acupuncture points.Health impairment is associated with changes in skin impedance at system-specific acupuncture points.Detection of skin impedance changes may assist in the early diagnosis of asthma and monitoring the effectiveness of therapeutic interventions for this condition.Method:This study compared skin impedance at acupuncture point Dingchuan(EX-B1),in 92 subjects with normal health(47 subjects,age 32.6 ±1.67yr) and those diagnosed with asthma(45 subjects,age 42.4 ±1.80 yr).Skin impedance was measured using a 2-electrode impedance meter bilaterally at EX-B1,0.5 "cun" lateral to the lower border of 7th cervical vertebra.Result:The study showed that skin impedance was significantly higher at acupuncture point EX-B1 in subjects with asthma(29.4 ± 21 kΩ) compared to subjects with normal health(13.8±7.9 kΩ)(P=0.013).Skin impedance was negatively correlated to forced expiratory volume in 1 second(FEV1,r=-0.59,P=0.012 in females;and r=-0.68,P=0.015 in males).A receiver operator characteristic(ROC) curve revealed an optimum cut-off point of 35 kΩ for male and 10 kΩ for female subjects.Conclusion:We conclude that EX-B1 skin impedance is higher in patients with asthma and skin impedance might be a possible adjunctive parameter for assisting diagnosis and monitoring asthmatic status.展开更多
Aim:In this study,we would like to determine associations between β2-Adrenergic Receptor(β2AR)polymorphisms at codon 16 and 27 and the response to short acting β2-agonist during asthmatic exacerbation.Methods:This ...Aim:In this study,we would like to determine associations between β2-Adrenergic Receptor(β2AR)polymorphisms at codon 16 and 27 and the response to short acting β2-agonist during asthmatic exacerbation.Methods:This was a prospective cross-sectional study of one year duration.One hundred and thirty two asthmatic patients were recruited.Five mls of venous blood was taken for DNA extraction and then genotyped for the β2AR polymorphisms using multiplex PCR.Patient's clinical responses to β2-agonist nebulization were then compared to their genotype to determine the association.Results:We found that there was no association between β2AR polymorphisms at both codon 16 and 27 with response towards short acting β2-agonist,P=0.315 and P=0.706 respectively.Conclusion:We suggested that β2AR polymorphisms at both codon 16 and 27 had no influent on the response to short acting β2-agonist.展开更多
目的观察咳喘镇定汤在小儿咳嗽变异性哮喘治疗中的作用及对患儿嗜酸性粒细胞计数(eosinophil count,EOS)、白介素-23(interleukin-23,IL-23)/辅助性T细胞17(helper T cells17,Th17)轴的影响。方法选取2020年8月—2023年2月收治的小儿咳...目的观察咳喘镇定汤在小儿咳嗽变异性哮喘治疗中的作用及对患儿嗜酸性粒细胞计数(eosinophil count,EOS)、白介素-23(interleukin-23,IL-23)/辅助性T细胞17(helper T cells17,Th17)轴的影响。方法选取2020年8月—2023年2月收治的小儿咳嗽变异性哮喘患儿104例,将患儿采用简单随机法分为两组。常规组给予止咳化痰、抗炎、平喘等常规治疗,咳喘镇定汤组在常规组基础上采用咳喘镇定汤辅助治疗。检测组间及组内T淋巴亚群、EOS、巨噬细胞炎症蛋白-1α(macrophage inflammatory protein-1α,MIP-1α)、Clara细胞分泌蛋白16(clara cell secreted protein 16,CC-16)、嗜酸细胞活化趋化因子(Eotaxin)、IL-23/Th17轴、小气道功能水平。评估组间及组内咳嗽症状评分、中医证候评分差异。统计组间疗效和不良反应。结果治疗前T淋巴亚群、CC-16、Eotaxin等差异无统计学意义(P>0.05)。两组治疗后CD_(8)^(+)、EOS、MIP-1α、Eotaxin降低,CC-16、CD_(4)^(+)、CD_(4)^(+)/CD_(8)^(+)升高,咳喘镇定汤组治疗后CD_(8)^(+)、EOS、MIP-1α、Eotaxin低于常规组,CC-16、CD_(4)^(+)、CD_(4)^(+)/CD_(8)^(+)高于常规组(P<0.05)。治疗前比较IL-23/Th17轴差异无统计学意义(P>0.05)。两组治疗后IL-23、Th17、白介素-17(interleukin-17,IL-17)降低,咳喘镇定汤组治疗后IL-23/Th17轴低于常规组(P<0.05)。治疗前相关评分无差异(P>0.05)。两组治疗后咳嗽症状评分、中医证候评分降低,咳喘镇定汤组治疗后咳嗽症状评分、中医症候评分低于常规组(P<0.05)。治疗前小气道功能无差异(P>0.05)。两组治疗后小气道功能升高,咳喘镇定汤组治疗后小气道功能高于常规组(P<0.05)。咳喘镇定汤组治愈13例,显效和有效共35例,总有效率92.31%高于常规组,差异有统计学意义(P<0.05)。结论咳喘镇定汤可通过调控小儿咳嗽变异性哮喘患儿IL-23/Th17轴,改善T淋巴亚群和小气道功能,减轻咳嗽症状,提高疗效。展开更多
基金The project supported by a NMRC grant NMRC/CBRG/0027/2012from the National Medical Research Council of Singapore,with additional support from the Singapore-MIT Alliance for Research and Technology
文摘OBJECTIVE To investigate the genome protective effects of anti-malaria drug,artesunate in an experimental allergic asthma model.METHODS Mice were sensitized on day 0 and 7 and challenged on day 14 with 100μg house dust mite(HDM)via intratracheal administration.Artesunate(30mg·kg-1)was administered intra-peritoneally on day 6,7,8,13,14 and 15.Samples were collected on day 1,3 and 5 post last HDM-challenge for analysis of air way inflammation and DNA damage.Lung sections were immunofluorescence(IF)-stained for DNA double strand breaks(DSBs)markers,γH2AX and 53BP1.Levels of DNA repair proteins Ku70 and Rad51,which are involved in non-homologous end joining(NHEJ)and homologous recombination(HR)DNA DSB repair pathways respectively,were measured.To quantify cell death in asthmatic lung,TUNEL staining was performed.Comet assay,a single cell gel electrophoresis was employed to detect DNA damage induced by HDM in BEAS-2Bhuman bronchial epithelial cell line,in vitro.RESULTS Artesunate treatment significantly reduces immune cells infiltration in BAL fluid of asthmatic mice,collected on day 3 and 5 post-challenge.Importantly,artesuante is able to protect bronchial epithelium from DNA DSBs induced by asthma,as detected by the reduced level of γH2AX and 53BP1 foci formation in the nucleus.This genome protective effect is evident even on day 1 post-challenge,when immune cells infiltration remained high.This indicates that artesunate confers protection on bronchial epithelium in the presence of inflammation.Additionally,artesunate is also able to reduce cell death in asthmatic lung revealed by TUNEL assay and cleaved caspase 3 level.Interestingly,the levels of DNA repair proteins in artesuante-treated asthmatic mice are unchanged as compared to HDM-only mice,suggesting that artesunate treatment does not augment the level of DNA repair proteins.When human bronchial epithelial BEAS-2 Bcells were exposed to HDMin vitro,we observed an increase in the levels of DNA damage.Artesunate(60μmol·L-1)co-incubated with HDM is not able to prevent direct DNA damage induced by the allergen.Together,these studies suggest that the genome protective effect of artesunate in vivo may be attributed to physiological effects(such as its anti-inflammatory effects)rather than serving to directly prevent DNA damage.CONCULSION This study highlights a novel role for artesunate in protecting bronchial epithelial cells from asthma-induced DNA damage.
基金National Natural Science Foundation of China (No: 21577045).
文摘Epidemiological studies have shown that there is a link between asthma and brain damage,but toxicological studies have not fully confirmed yet,especially the effects of asthma on the brain. In this study,at first,we explore the effects of asthma on the brain through the establishment of an allergic asthma model. Then PM_(2.5),a typical outdoor air pollutant and formaldehyde,a typical indoor air pollutant were selected to be closer to the true environment and find whether there is any synergism between them. In this study,an ovalbumin( OVA)-sensitized mice asthma model was established. 30 male Balb/c mice were randomly divided into 5 groups:( 1) saline control group,( 2) OVA-sensitized group,( 3) OVA-combined with formaldehyde exposure group,( 4) OVA-combined with PM_(2.5) exposure group,( 5) Combination of OVA,formaldehyde and PM_(2.5) exposure group. The mice were inhaled with formaldehyde or/and instilled with PM_(2.5) from day 1 to 18. The mice asthma model was developed by OVA sensitization and challenge. The mice were sensitized with OVA+Al( OH)3( 5 mg OVA and 175 mg Al( OH)3 in 30 m L saline each time) or saline( 30 m L saline each time) by intraperitoneal injection on day 1,7 and 14.This was then followed by an aerosol challenge in 1% OVA( 30 min·d^(-1)) from day 19 to 25( 7 times) using an ultrasonic nebulizer. On the 26 th day,the organ coefficient of mice brain was counted,then the contents of oxidative stress of mice brain were measured,including reactive oxygen species( ROS),glutathione( GSH) and malondialdehyde( MDA),and the concentrations of NF-κB and interleukin-1β( IL-1β) were detected by using ELISA kits.Detection of interleukin-6( IL-6) was made with immunohistochemical method. Histological assay for brain was also conducted. In our results,all the OVA treated groups showed a significant increase of ROS and a significant decrease of GSH contents when compared with the control group. Except OVA-sensitized group,other OVA treated groups also showed a significant increase of MDA contents when compared with the control group,and MDA contents of OVA-sensitized group showed significant change when compared to the combined exposure group. In ROS and GSH,combined exposure showed some joint effect compared with single exposure. When OVA was applied in combination with formaldehyde and PM_(2.5),NF-κB was activated. And all the OVA treated groups showed increased levels of IL-1β and IL-6 compared with the control group. And the combined exposure showed an aggravated effect when compared with OVA-sensitized group. Histopathological observation of the hippocampus in mice brain clearly showed the difference of eosin( EO) stained neurons in the combined exposure group compared with the control group and OVA-sensitized group. The pyramidal neurons of the mice with allergic asthma exposed to formaldehyde and/or PM_(2.5) had been reduced in number,the cells were swollen and the dendrites had disappeared. Allergic asthma can cause damage to the brain through oxidative stress. Exposure to formaldehyde and PM_(2.5) will increase the damage caused by allergic asthma to the brain,which may be mediated by oxidative stress and NF-κB activation.This promotes the release of the inflammatory factors,resulting in increased inflammation.
基金The project supported by University Grant Commission,New Delhi(P-01/634)
文摘OBJECTIVE The study aims to evaluate intranasal(i.n.)curcumin at 5mg·kg-1,its absorption through nasal mucosa reaching blood and lungs and investigate its anti-allergic and anti-asthmatic potentiality in ameliorating ovalbumin induced asthma in mouse model.METHODS A simple and sensitive high performance liquid chromatography method using UV detection(HPLC-UV)was developed and validated for the determination of nasal curcumin 5mg·kg-1 in nasal mucosa,plasma and lungs from 15min-6hof post dosing and further applied to determine the pharmacokinetics parameter.Further,for the anti-asthmatic study,BALB/c mice were sensitized(day 1,7and 14)and challenged with ovalbumin(day 19-22)and treated with intranasal curcumin 5mg·kg-1(in the form of nasal drops)before an hour of challenge(day 19-22)to investigate its therapeutic effect on various parameters of airway inflammation as detected in the bronchoalveolar lavage fluid,serum and lung tissue.Serum was also used to study the liver kidney function test for the toxicity.RESULTS The validated method of HPLC was sensitive with a lower limit of quantitation of 5μg·mL-1 and the calibration curve represented good linearity(r2≥0.999)over the linear range of 5-50μg·mL-1.HPLC study reveals,absorption and quantification of curcumin as 1.9μg·mL-1 in the nasal mucosal scrapping at 15 min elevating to 4.9μg·mL-1 till 1h and declining to 3.2μg·mL-1 till 3h after intranasal administration of curcumin(5mg·kg-1).The plasma showed 0.9μg·mL-1 after 15 min spiking upto 1.5μg·mL-1 till 3h while lung homogenate retained up to 3.6μg·mL-1 of curcumin till 3h,which was detectable from 15min(0.27μg·mL-1)and was on higher side as compared to earlier studies.The same pharmacological dose(5mg·kg-1,i.n.)has shown anti-asthmatic potential by inhibiting airway inflammation(eosinophilic inflammation),bronchoconstriction and modulation in cytokines level of Th2(IL-4,IL-5),Th1(IFN-γ)and proinflammatory(TNF-α)cytokines in ovalbumin induced asthma without having any side effect as detected by liver kidney function test.CONCLUSION The study reveals nasal mucosa as a viable route for the absorption of intranasal curcumin and accommodating increased transportation to the blood and lungs.Also,the nasal route is effective in retaining the level of curcumin till 6h without any degradation and hence could be a promising route to improve its biological activities.Present study may prove the possibility of curcumin as complementary medication in the development of nasal drops or through nebulizer in human subjects.Further,pharmacodynamic study is in progress to prove its effectiveness not only in pulmonary disorders but also for systemic disorders.
文摘OBJECTIVE Airway wall remodeling(AWR),which refers to structural changes in the airway,is a key characteristic of asthma.Airway smooth muscle(ASM)cell hypertrophy and hyperplasia contributes to AWR.Glucocorticoids,which are used as first line therapy for the treatment of asthma,reduce ASM proliferation but the magnitude of their anti-proliferative actions is dependent on the mitogen used.Moreover,glucocorticoid therapy is accompanied by many side effects.Artesunate,a semi-synthetic artemisinin derivative,has been widely used to treat malaria with minimal toxicity.Artesunate has been shown to attenuate allergic airway inflammation in mice.However,its role in treating AWR in asthma is not known.In this study,we hypothesize that artesunate has anti-proliferative actions on ASM cells,potentially reversing AWR.METHODS and RESULTS Quiescent primary human ASM cells were pre-treated(1h)with artesunate(3,10,30μmol·L-1)before being stimulated with either FBS(10%)or thrombin(0.3U·mL-1).Following 48 h stimulation with mitogen,cells were counted using a haemocytometer.Dexamethasone(Dex,100nmol·L-1)was used as a positive control.Artesunate concentration-dependently reduced cell number and the magnitude of inhibition appeared to be non-mitogen dependent.Moreover,we examined the effect of artesunate on two important signalling proteins involved in cell proliferation,ERK1/2phosphorylation and cyclin D1 protein levels.Artesunate reduced cyclin D1 protein levels significantly following 20 h stimulation with either thrombin or FBS but had no effect on ERK1/2 phosphorylation following 6h stimulation.Importantly,artesunate(30μmol·L-1),but not Dex,inhibited the phosphorylation of Akt,which is upstream of cyclin D1.Next,we show that the inhibitory effect of artesunate,but not Dex,on ASM cell number is retained at least 24h post-treatment following stimulation with FBS.In an acute murine model of allergic asthma,artesunate treatment decreased sm-α-actin positive cells and cyclin D1 protein abundance in the ovalbumin sensitized and challenged mice.CONCLUSION We have shown that artesunate regulates the PI3K/Akt pathway to inhibit the proliferation of primary human cultured ASM cells.This is an alternative mode of action,in comparison to glucocorticoids such as Dex.The anti-proliferative effect of artesunate was further validated in vivo.Thus,our study provides a basis for the future development of artesunate as a novel anti-AWR agent that targets ASM hyperplasia via the PI3K/Akt pathway.Moreover,artesunate may be used as an add-on therapy for asthmatic patients.
基金supported by National Natural Science Foundation of China(11172340)Training Program for Hundreds of Distinguished Leading Scientists of Chongqing,Specialized Research Fund for the Doctoral Program of Higher Education of China(20120191120032)
文摘Targeted peptides have been identified as showing great promise for treatment of various diseases including asthma.Asthma is considered of difficuIt-to-treat due to its unclear etiology,thus usually requiring life-long treatment.Current strategies for asthma therapy are hampered with undesirable side effects,poor targeting and failure in modulating airway hyperresponsiveness,leading to pressing need of developing more targeted and effective therapeutic sites for asthma.Recently,a disintegrin and metalloproteinase 8(ADAM8)have been shown to over-
基金supported by National Natural Science Foundation of China(Grant No. 11172340)Training Program for Hundreds of Distinguished Leading Scientists of Chongqing+3 种基金Chongqing Natural Science Foundation(Grant No.CSTC2010BA5001,CSTC2012jjA0588)Fundamental Research Funds for the Central Universities(Grant No.CQDXWL-2012-123)Specialized Research Fund for the Doctoral Program of Higher Education of China(Grant No.20120191120032)Sharing Fund of Chongqing University's LargeScale Equipment(Grant No.2010063057,2011063048,2011063049)
文摘Introduction Excessive narrowing of airways is the most important pathological feature of asthma,but its mechanism remains puzzling.One certain thing is that the contraction of airway smooth muscle(ASM)ultimately causes airway narrowing,thus both structural and functional alterations of airway smooth muscle(ASM)are thought as common final pathway responsible for the bronchial hyperresponsiveness(BHR),the hall mark of asthma.Many chemical and physical factors such as air pollutants,inflammatory agents,mechanical and geometrical properties of the microenvironment could influence structure and/or function of ASM cells.In addition,some re-
文摘Prevention and treatment of 88 cases of asthma with acupoint application therapy.Analyses of the mechanism of treatment according to the Traditional Chinese Medicine(TCM)theory and laboratory test results.
文摘Objective:To assess the haematological and lipid profile assays in asthmatics.Methods: Eighty asthmatic subjects were prospectively studied in a major referral centre serving the Niger Delta region of Nigeria for 12 months(2006-2007).Clinico-haematological and serum lipid total cholesterol(TC),triglyceride(TG),and lipoproteins concentration were analyzed after adjusting for age,cigarette smoking,alcohol ingestion,hypertension and diabetes mellitus.Results: Eighty patients(34 males and 46 females) were seen with female predominating in the various age groups(M∶F ratio,0.7∶1).Total cholesterol and low density lipoproteins-cholesterol for the asthmatics was significantly higher than the controls(P<0.000 1),while the ratio of TC∶HDL-C(high density lipoprotein-cholesterol) in asthmatics was 3.67 compared to the control value of 3.01.TC and low density lipoprotein-cholesterole(LDL-C) were significantly higher in females than the males(P<0.05).There was a combined hypertriglyceridemia(HT,>2.3mmol/L) and a significant hypercholesterolemia(HC,>5.2mmol/L) according to the Adult Treatment Panel III definition in asthmatics thereby putting them at increased risk for the development of cardiovascular disease as well as other disorders related to excess lipids.There was a significant thrombocytopenia(P<0.000 1) which may accompany allergen exposure and this persists for 24 h;that asthmatics of African descent showed a significantly increased total leucocyte count(P=0.001) similar to other studies in the Western countries.Conclusion: Hyperlipidaemia is a prevalent medical problem among asthmatics;hence screening for fasting serum lipid levels to identify those who need early intervention is recommended.
文摘Objective: The aim of this study was to assess school indoor exposure to microbial products and prevalence of asthma and allergies in rural and urban children.Methods: This study was carried on a rural and an urban school.Environmental endotoxin level was measured in multiple samples of the ambient indoor air dust collected on special aseptic filter papers from the two schools.For two hundred children history taking,clinical examination,allergen skin prick test and basic pulmonary function test were preformed.Results: Environmental endotoxin levels showed significantly higher mean values(P<0.01) in rural school(3 EU/mg) as compared to the urban school(0.1 EU/mg) with(OR=5.163;95% CI: 0.95-28).History of allergic symptoms was significantly more in urban than rural students(P=0.01).Mean values of pulmonary function parameters were significantly lower values in urban students compared to rural students.Skin prick test results showed significant reactions to all tested allergens in urban children compared to rural children(P<0.05).Conclusion: There is an inverse association between environmental exposure to endotoxins and susceptibility for allergic manifestations in school children.
基金supported by National Natural Science Foundation of China (81260490)
文摘OBJECTIVE Using bronchial asthma rats,to observe the effects of Smooth wheezing effect of polysaccharide.In addition,to study the effects of COM in different bronchial asthma model.METHODS Bronchial rats established by ovalbumin(OVA),were randomly divided into different group.Every other week building reference literature intraperitoneal injection of OVA,21 d after injection of 3 consecutive ultrasonic atomization inhalation of 1% OVA stimulating 30 d,stimulate the 31 d began to medicine.Lavage for 4 weeks ELISA test ratio of IgE,SP-A,IL-4 and IL-5 was serum and bronchoal veolar lavage fluid etc.Data was in x±s tabular format,SPSS16.0 statistics software is used to perform statistical analysis on the data,and P<0.05 shows meaningful statistical difference.RESULTS Quince polysac.charide can reduce the IgE,IL-4 level and elevated the SP-A,IL-5 level in serum and bronchoal veolar lavage fluid.CONCLUSION Quince polysaccharide has antiasthmatic effect on bronchial asthma rats.
文摘Objective:Asthma can be a disabling disease and despite advances in pharmacology,the prevalence of this condition globally remains high and accounts for a significant proportion of public health care costs.While pharmacology is the mainstay of asthma management,drug side effects have promoted alternative therapeutic interventions,such as acupuncture.Acupuncture points have a lower skin impedance compared to non-acupuncture points.Health impairment is associated with changes in skin impedance at system-specific acupuncture points.Detection of skin impedance changes may assist in the early diagnosis of asthma and monitoring the effectiveness of therapeutic interventions for this condition.Method:This study compared skin impedance at acupuncture point Dingchuan(EX-B1),in 92 subjects with normal health(47 subjects,age 32.6 ±1.67yr) and those diagnosed with asthma(45 subjects,age 42.4 ±1.80 yr).Skin impedance was measured using a 2-electrode impedance meter bilaterally at EX-B1,0.5 "cun" lateral to the lower border of 7th cervical vertebra.Result:The study showed that skin impedance was significantly higher at acupuncture point EX-B1 in subjects with asthma(29.4 ± 21 kΩ) compared to subjects with normal health(13.8±7.9 kΩ)(P=0.013).Skin impedance was negatively correlated to forced expiratory volume in 1 second(FEV1,r=-0.59,P=0.012 in females;and r=-0.68,P=0.015 in males).A receiver operator characteristic(ROC) curve revealed an optimum cut-off point of 35 kΩ for male and 10 kΩ for female subjects.Conclusion:We conclude that EX-B1 skin impedance is higher in patients with asthma and skin impedance might be a possible adjunctive parameter for assisting diagnosis and monitoring asthmatic status.
基金This project was carried out under the financial support of USM short-term grant(304/PPSP/6131324)
文摘Aim:In this study,we would like to determine associations between β2-Adrenergic Receptor(β2AR)polymorphisms at codon 16 and 27 and the response to short acting β2-agonist during asthmatic exacerbation.Methods:This was a prospective cross-sectional study of one year duration.One hundred and thirty two asthmatic patients were recruited.Five mls of venous blood was taken for DNA extraction and then genotyped for the β2AR polymorphisms using multiplex PCR.Patient's clinical responses to β2-agonist nebulization were then compared to their genotype to determine the association.Results:We found that there was no association between β2AR polymorphisms at both codon 16 and 27 with response towards short acting β2-agonist,P=0.315 and P=0.706 respectively.Conclusion:We suggested that β2AR polymorphisms at both codon 16 and 27 had no influent on the response to short acting β2-agonist.
文摘目的观察咳喘镇定汤在小儿咳嗽变异性哮喘治疗中的作用及对患儿嗜酸性粒细胞计数(eosinophil count,EOS)、白介素-23(interleukin-23,IL-23)/辅助性T细胞17(helper T cells17,Th17)轴的影响。方法选取2020年8月—2023年2月收治的小儿咳嗽变异性哮喘患儿104例,将患儿采用简单随机法分为两组。常规组给予止咳化痰、抗炎、平喘等常规治疗,咳喘镇定汤组在常规组基础上采用咳喘镇定汤辅助治疗。检测组间及组内T淋巴亚群、EOS、巨噬细胞炎症蛋白-1α(macrophage inflammatory protein-1α,MIP-1α)、Clara细胞分泌蛋白16(clara cell secreted protein 16,CC-16)、嗜酸细胞活化趋化因子(Eotaxin)、IL-23/Th17轴、小气道功能水平。评估组间及组内咳嗽症状评分、中医证候评分差异。统计组间疗效和不良反应。结果治疗前T淋巴亚群、CC-16、Eotaxin等差异无统计学意义(P>0.05)。两组治疗后CD_(8)^(+)、EOS、MIP-1α、Eotaxin降低,CC-16、CD_(4)^(+)、CD_(4)^(+)/CD_(8)^(+)升高,咳喘镇定汤组治疗后CD_(8)^(+)、EOS、MIP-1α、Eotaxin低于常规组,CC-16、CD_(4)^(+)、CD_(4)^(+)/CD_(8)^(+)高于常规组(P<0.05)。治疗前比较IL-23/Th17轴差异无统计学意义(P>0.05)。两组治疗后IL-23、Th17、白介素-17(interleukin-17,IL-17)降低,咳喘镇定汤组治疗后IL-23/Th17轴低于常规组(P<0.05)。治疗前相关评分无差异(P>0.05)。两组治疗后咳嗽症状评分、中医证候评分降低,咳喘镇定汤组治疗后咳嗽症状评分、中医症候评分低于常规组(P<0.05)。治疗前小气道功能无差异(P>0.05)。两组治疗后小气道功能升高,咳喘镇定汤组治疗后小气道功能高于常规组(P<0.05)。咳喘镇定汤组治愈13例,显效和有效共35例,总有效率92.31%高于常规组,差异有统计学意义(P<0.05)。结论咳喘镇定汤可通过调控小儿咳嗽变异性哮喘患儿IL-23/Th17轴,改善T淋巴亚群和小气道功能,减轻咳嗽症状,提高疗效。
