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Curcumin Inhibits Lipopolysaccharide-lnduced mucin 5AC Hypersecretion and Airway Inflammation via Nuclear Factor Erythroid 2-Related Factor 2

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Chinese Medical Journal 2018年第14期131卷 1686-1693页

作者： Xiao-Ping Lin Cheng Xue Jia-Min Zhang Wei-Jing Wu Xiao-Yang Chen Yi-Ming Zeng Department of Pulmonary and Critical Care Medicine The Second Affiliated Hospital of Fujian Medical University Quanzhou Fujian 362000 China Respiratory Medicine Center of Fujian Province Quanzhou Fujian 362000 China

Background： Excess mucus production is an important pathophysiological feature of chronic inflammatory airway diseases. Effective therapies are currently lacking. The aim of the study was to evaluate the effects ofcurcumin （CUR） on lipopolysaccharide （LPS）-induced mucus secretion and inflammation, and explored the underlying mechanism in vivo and in vitro. Methods： For the in vitro study, human bronchial epithelial （NCI-H292） cells were pretreated with CUR or vehicle for 30 min, and then exposed to LPS for 24 h. Next, nuclear factor erythroid 2-related factor 2 （Nrf2） was knocked down with Nrf2 small interfering RNA （siRNA） to confirm the specific role of Nrf2 in mucin regulation of CUR in NCI-H292 cells. In vivo, C57BL/6 mice were randomly assigned to three groups （n = 7 for each group）： control group, LPS group, and LPS ＋ CUR group. Mice in LPS and LPS ＋ CUR group were injected with saline or CUR （50 mg/kg） intraperitoneally 2 h before intratracheal instillation with LPS （ 100 μg/ml） for 7 days. Cell lysate and lung tissue were obtained to measured mucin 5AC （MUC5ac） and Nrf2 mRNA and protein expression by a real-time polymerase chain reaction and Western blotting. Bronchoalveolar lavage fluid （BALF） was collected to enumerate total cells and neutrophils. HistopathologicaI changes of the lung were observed. Data were analyzed by one-way analysis of variance. Student＇s t-test was used when two groups were compared. Results： CUR significantly decreased the expression ofMUC5ac mRNA and protein in NCI-H292 cells exposed to LPS. This effect was dose dependent （2.424 ± 0.318 vs. 7.169 ± 1.785, t = 4.534, and 1.060 ± 0.197 vs. 2.340 ± 0.209, t = 7.716; both P 〈 0.05, respectively） and accompanied by increased mRNA and protein expression of Nrf2 （1.952 ± 0.340 vs. 1.142 ± 0.176, t = -3.661, and 2.010 ± 0.209 vs. 1.089 ±0. 132, t = -6.453; both P 〈 0.05, respectively）. Furthermore, knockdown of Nrf2 with siRNA increased MUC5A C mRN A expression by 47.7%, compared with levels observed in the siRNA-negative group （6.845 ±

关键词： Airway mucin Curcumin mucin 5AC Nuclear Factor Erythroid 2-Related Factor 2

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黏液-纤毛标志物mucin 5AC-acetylated alpha-tubulin在过敏性鼻炎患者鼻黏膜中的表达

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中国临床新医学 2023年第1期16卷 31-36页

作者：郭沐涛周穗子邱前辉南方医科大学附属广东省人民医院(广东省医学科学院)耳鼻咽喉头颈外科广州510080

目的探究过敏性鼻炎(AR)患者鼻腔黏液-纤毛清除功能在鼻黏膜分子水平上的损伤表现和严重程度。方法选取2021年3月至2022年3月期间在我院进行鼻中隔偏曲手术的40例患者的下鼻甲黏膜组织,其中AR患者21例(AR组),非AR患者(对照组)19例。通... 详细信息

目的探究过敏性鼻炎(AR)患者鼻腔黏液-纤毛清除功能在鼻黏膜分子水平上的损伤表现和严重程度。方法选取2021年3月至2022年3月期间在我院进行鼻中隔偏曲手术的40例患者的下鼻甲黏膜组织,其中AR患者21例(AR组),非AR患者(对照组)19例。通过免疫荧光染色方法在蛋白水平上观察及评估黏液分泌标志物mucin 5AC(MUC5ac)和纤毛标志物acetylated alpha-tubulin(acet.α-tubulin)表达情况。结果与对照组相比,AR组黏液分泌的总免疫荧光强度增加32.365%,纤毛长度缩短将近1/2,纤毛脱落评分上升将近3倍,纤毛总免疫荧光强度下降24.555%。结论AR患者黏液分泌量显著增加,纤毛排列不齐、变短、稀疏以及脱落增加可能是导致AR患者鼻腔黏膜黏液-纤毛清除功能减弱,继而加重AR症状严重程度的分子依据。

关键词：过敏性鼻炎黏液-纤毛清除功能 mucin 5AC acetylated alpha-tubulin

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血清胃泌素、胃蛋白酶原及mucin 5AC蛋白表达与胃息肉恶变关系的研究

血清胃泌素、胃蛋白酶原及Mucin 5AC蛋白表达与胃息肉恶变关系的...

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作者：粟春林川北医学院

学位级别：硕士

目的:探讨血清胃泌素、胃蛋白酶原及mucin 5AC蛋白的表达与胃息肉恶变的关系及其临床意义。方法:本研究设立实验组:胃息肉患者108例,对照组:健康志愿者41例。采用放射免疫法（radioimmunoassav,RIA）、时间分辨荧光免疫法（timeresolved... 详细信息

目的:探讨血清胃泌素、胃蛋白酶原及mucin 5AC蛋白的表达与胃息肉恶变的关系及其临床意义。方法:本研究设立实验组:胃息肉患者108例,对照组:健康志愿者41例。采用放射免疫法（radioimmunoassav,RIA）、时间分辨荧光免疫法（timeresolved fluoroimmunoassay,TRFIA）分别检测各组空腹血清胃泌素（serum gastrin,SG）、胃蛋白酶原Ⅰ（pepsinogenⅠ,PGⅠ）和胃蛋白酶原Ⅱ（pepsinogenⅡ,PGⅡ）水平,计算PGⅠ/PGⅡ比值（PGR）;运用免疫组化方法（immunohistochemical,IHC）检测正常胃粘膜、胃底腺息肉、增生性息肉、腺瘤性息肉和胃癌等组织中mucin 5AC蛋白的表达。结果:1、实验组SG水平（67.76±34.21pg/ml）明显高于对照组（50.97±23.65pg/ml）,差异具有统计学意义（t=3.394,P=0.001）。2、实验组SG水平根据不同病理类型（F=4.21,P=0.007）、大小（F=4.02,P=0.02）、数目（F=5.11,P=0.007）、部位（F=5.21,P=0.002）与对照组比较差异均有统计学意义。3、胃底腺息肉PGⅠ水平与PGR明显高于腺瘤性息肉,差异具有统计学意义（P＜0.05）。4、正常胃粘膜、胃底腺息肉、增生性息肉mucin 5AC蛋白表达明显高于胃腺癌组织,差异具有统计学意义（P＜0.05）;胃底腺息肉、增生性息肉mucin 5AC蛋白表达明显高于腺瘤性息肉,差异具有统计学意义（P＜0.05）。结论:1、各种类型胃息肉患者的血清胃泌素水平均高于正常对照,且与胃息肉发生、部位、大小、数目均相关,腺瘤性息肉与血清胃泌素关系更密切;2、胃息肉患者的血清胃蛋白酶原水平高于正常对照,但腺瘤性息肉组低于正常对照,具体关系有待扩大样本进一步研究;3、检测mucin 5AC蛋白表达可能对预测胃息肉癌变有重要价值;4、联合检测血清胃泌素、胃蛋白酶原与mucin 5AC蛋白表达可能在胃息肉发生与癌变过程中具有重要临床意义,可能为胃息肉患者治疗及临床随访提供临床依据。

关键词：胃泌素胃蛋白酶原 mucin 5AC 胃息肉

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High mucin 5AC expression predicts adverse postoperative recurrence and survival of patients with clear-cell renal cell carcinoma

High mucin 5AC expression predicts adverse postoperative rec...

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2017年中国肿瘤标志物学术大会暨第十一届肿瘤标志物青...

作者： Haijian Zhang Dengfu Yao Jiejie Xu Jianxin Gu Research Center of Clinical Medicine Affiliated Hospital of Nantong University Department of Biochemistry and Molecular Biology School of Basic Medical SciencesFudan University Department of Urology Fudan University Shanghai Cancer Center

Background: mucin 5 ac（MUC5 ac）, as a member of secreted/gel-forming mucin family, was frequently found to be abnormally expressed in inflammation or malignant diseases. However, the clinic pathologic features and prognostic values of MUC5 ac in clear cell renal cell carcinoma（ccRCC） have not been reported up to now. Methods: MUC5 ac expression was analyzed by immunohistochemistry on tissue microarrays. KaplanMeier survival curves, Univariate and Multivariate Cox analysis and newly-established nomogram model were performed to evaluate the prognostic value. Results: MUC5 ac expression was firstly found to be up-regulated in patients with ccRCC, positively associated with tumor size, pN stage, lymphovascular invasion, Fuhrman grade, rahbdoid differentiation, sarcomatoid features, tumor necrosis, ECOG-PS and recurrence. Furthermore, MUC5 ac expression might be contributed to risk stratification of ccRCC patients with TNM stage Ⅲ+Ⅳ or Fuhrman grade 3 or 4 for overall survival（OS） and recurrence-free survival（RFS） analysis, and it was demonstrated to be negatively correlated with OS and RFS of ccRCC patients. What’s more, MUC5 ac was identified as a potential independent adverse prognostic factor;prediction accuracy of MUC5 ac-based new nomogram model was drastically improved for OS and RFS of ccRCC patients. Conclusion: MUC5 ac is a promising independent adverse prognostic factor for ccRCC patients, it maybe conducive to postoperative risk stratification and guide treatment in the future.

关键词： mucin 5AC clear cell renal cell carcinoma overall survival recurrence-free survival prognostic biomarker

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Qingfei oral liquid downregulates TRPV1 expression to reduce airway inflammation and mucus hypersecretion injury caused by respiratory syncytial virus infection and asthma in mice

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Traditional Medicine Research 2020年第4期5卷 229-237页

作者： Xiao-Ping Jing Wu-Ning Yan Wei-Wei Cheng Hai-Rong Zeng Department of Traditional Chinese Medicine Shanghai Children’s HospitalShanghai Jiao Tong UniversityShanghai 200062China

Objective:Qingfei oral liquid(QF),an experimental Chinese medicine prescription developed from the ancient priscription of traditional Chinese medicines Ma Xin Shi Gan decoction and Tingli Dazao Xie Fei decoction,has been effectively used since decades to treat patients with viral pneumonia and asthma.In our previous study,we had demonstrated that QF can significantly reduce airway hyperresponsiveness,hyperemia,lung tissue edema,inflammatory lung tissue infiltration in mice,airway mucus secretion,and peripheral airway collagen hyperplasia;however,its mechanism of action is unknown.Methods:Fifty 6–8-week-old male BALB/c mice were equally and randomly divided into five groups:the control,ovalbumin(OVA),OVA+respiratory syncytial virus(RSV),QF,and dexamethasone(Dxms)groups.The QF group was administered QF at 1.17 g·kg−1·d−1,the Dxms group received dexamethasone injections at 0.2 mg·kg−1·d−1,and the remaining groups were administered PBS.Inflammation in the lung tissue was assessed by hematoxylin and eosin(HE),periodic acid–Schiff(PAS),and Van Gieson staining.ELISA was used to evaluate the IL-13,IL-25,and IL-33 in the mice.Western blotting was used to examine changes in the proteins levels of transient receptor potential vanilloid-1(TRPV1)and mucin 5AC(MUC5ac)in the lung tissues of mice.Results:Histopathological evaluation revealed that the OVA and OVA+RSV groups exhibited lung tissue edema and inflammatory lung tissue infiltration in the HE staining and airway secretions in the PAS staining;collagen hyperplasia around the airway was increased in these two groups compared with the control group.The QF group exhibited significantly reduced lung tissue edema,inflammatory lung tissue infiltration,airway secretions,and collagen hyperplasia around the airway compared with the OVA+RSV group.We analyzed the serum levels of IL-13,IL-25,and IL-33 in the mice and found that these levels were higher in the OVA and OVA+RSV groups than in the control group(P5 in the OVA group,P<0.01 in the OVA+RSV group).The QF group exhibited

关键词： Qingfei oral liquid Viral pneumonia Asthma Respiratory syncytial virus infection Transient receptor potential vanilloid-1 mucin 5AC

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Increased expression of human calcium-activated chloride channel 1 is correlated with mucus overproduction in the airways of Chinese patients with chronic obstructive pulmonary disease

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Chinese Medical Journal 2007年第12期120卷 1051-1057页

作者： WANG Ke FENG Yu-ling WEN Fu-qiang CHEN Xue-rong OU Xue-mei XU Dan YANG Jie DENG Zhi-pin Division of Pulmonary Diseases State Key Laboratory of Biotherapy of China and Department of Respiratory Medicine West China Hospital of Sichuan University Chengdu 610041 China

Background Chronic obstructive pulmonary disease （COPD） is usually complicated with mucus overproduction in airway. Recently the increased expression of the human calcium-activated chloride channel 1 （CacC1） was found to play an important role in mucus overproduction in the asthmatic airways. To investigate the relationship of CacC1 and mucus overproduction in the airway of Chinese patients with COPD, the expressions of CacC1, MUC5ac and mucus in bronchial tissues were examined. Methods Bronchial tissues were obtained from fiberoptic bronchoscopy and bronchial biopsy in West China Hospital from April to July in 2004. Twenty-five patients were diagnosed as the patients with COPD overproduction, and other 20 were the control subjects. The expressions of CacC1, MUC5ac and mucin in bronchial tissues were detected by reverse transcriptase-polymerase chain reaction （RT-PCR）, in situ hybridization with digoxigenin （DIG）-Iabeled RNA probe, immunohistochemical and alcian blue-periodic acid Schiff （AB-PAS） staining, respectively. Results Compared with the control group, the stronger expressions of CacC1 were further detected throughout the bronchial tissues from patients with COPD （P〈0.01）. Furthermore, the stronger expressions of the CacC1 mRNA were related to the severity of airflow obstruction. Samples from COPD showed a stronger staining for MUC5ac than those in control subjects （P〈0.01） and AB-PAS staining revealed more mucins in COPD patients＇ submucosal gland comparing with that in control subjects （P〈0.01）. Expression levels of the CacC1 mRNA were respectively negatively correlated with the patients＇ forced expiratory volume in one second （FEV~） / forced vital capacity （FVC） data, FEV1% predicted data, V50% predicted data, V25% predicted data （r=-0.43, r=-0.43, r=-0.35, r=-0.36, P〈0.01, P〈0.01, P〈0.05, P〈0.05）. While the expression levels of the CacC1 mRNA were well correlated with the expression levels of the MUC5ac mRNA of airway epithelium and the PAS-AB stained area of submucosal glands （r=0.39, r=0.46, P〈0

关键词： calcium-activated chloride channel 1 mucin 5AC mucin mucus overproduction chronic obstructive pulmonary disease

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Decreased expression of human aquaporin-5 correlated with mucus overproduction in airways of chronic obstructive pulmonary disease

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acta Pharmacologica Sinica 2007年第8期28卷 1166-1174页

作者： Ke WANG Yu-lin FENG Fu-qiang WEN~2 Xue-rong CHEN Xue-mei OU Dan XU Jie YANG Zhi-ping DENG Division of Pulmonary Diseases,State Key Laboratory of Biotherapy of China,and Department of Respiratory Medicine,West China Hospital of Sichuan University,Sichuan 610041,China Division of Pulmonary Diseases State Key Laboratory of Biotherapy of Chinaand Department of Respiratory MedicineWest China Hospital of Sichuan UniversitySichuan 610041China

Aim:To investigate the relationship between aquaporin-5(AQP5)expression andmucus overproduction in the airways of Chinese patients with chronic obstruc-tive pulmonary disease(COPD)and the correlation with pulmonary functionchange.Methods:Bronchial tissues were obtained from fiberoptic bronchoscopyand bronchial biopsy in West China Hospital from April to July 2004.Twenty-fivepatients were diagnosed as COPD patients,and another 20 were diagnosed as thecontrol patients.The expressions ofAQP5,mucin 5AC(MUC5ac),and mucin inbronchial tissues were detected by semiquantitative RT-PCR,in situ hybridization,and immunohistochemical and alcian blue-periodic acid-Schiff(AB-PAS)staining,respectively.Results:Compared with the control group,an attenuated expres-sion of AQP5was detected throughout the bronchial tissues from patients withCOPD(P0.05).Simultaneously,increased staining of MUC5ac and mucus in submucosal glandswere noted(P5and increased the staining of MUC5ac and mucus in submucosal glands in theCOPD groups(P0.05).The decreased expression of AQP5mRNA was correlatedwith forced expiratory volume in 1 s(FEV1)/forced vital capacity(FVC)(r=0.60,P50%vital capacity(V50)% predicted value(r=0.55,P5% vital capacity(V25)% predicted value(r=0.45,P5ac mRNA of the epitheliumairways(r=-0.45,P5ac mRNA correlated with the posi-tively AB-PAS-stained area of submucosal glands and correlated negativelywith FEV1/FVC(r=-0.53;P53;P50%predicted value(r=-0.48;P5% predicted value(r=-0.43;P<0.01).Conclusion:The attenuated gene express

关键词： aquaporin-5 mucin 5AC mucin mucus overproduction chronic obstructive pulmonary disease

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