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Surfactant protein D inhibits lipid-laden foamy macrophages and lung inflammation in chronic obstructive pulmonary disease

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Cellular & Molecular Immunology 2023年第1期20卷 38-50页

作者： miao-hsi hsieh Pei-Chi Chen Han-Yin Hsu Jui-Chang Liu Yu-Sheng Ho Yuh Jyh Lin Chin-Wei Kuo Wen-Shuo Kuo Hui-Fang Kao Shulhn-Der Wang Zhi-Gang Liu Lawrence Shih-hsin Wu Jiu-Yao Wang Center for Allergy Immunologyand Microbiome(A.I.M.)China Medical University HospitalTaichungTaiwanChina Graduate Institute of Basic Medical Sciences College of MedicineNational Cheng Kung UniversityTainanTaiwanChina Department of Nursing National Tainan Junior College of NursingTainanTaiwanChina Graduate Institute of Biochemistry and Molecular Biology College of MedicineNational Cheng Kung UniversityTainanTaiwanChina Department of Pediatrics National Cheng Kung University HospitalTainanTaiwanChina Division of Pulmonary Medicine Department of Internal MedicineNational Cheng Kung University HospitalCollege of MedicineNational Cheng Kung UniversityTainanTaiwanChina Institute of Clinical Medicine College of MedicineNational Cheng Kung UniversityTainanTaiwanChina School of Chemistry and Materials Science Nanjing University of Information Science and TechnologyNanjingChina School of Post-Baccalaureate Chinese Medicine China Medical UniversityTaichungTaiwanChina Department of Respirology and Allergy Third Affiliated Hospital of Shenzhen UniversityShenzhenChina Institute of Biomedical Sciences China Medical UniversityTaichungTaiwanChina Department of Allergy Immunologyand Rheumatology(AIR)China Medical University Children’s HospitalTaichungTaiwanChina

Increased levels of surfactant protein D (SP-D) and lipid-laden foamy macrophages (FMs) are frequently found under oxidative stress conditions and/or in patients with chronic obstructive pulmonary disease (COPD) who are also chronically exposed to cigarette smoke (CS). However, the roles and molecular mechanisms of SP-D and FMs in COPD have not yet been determined. In this study, increased levels of SP-D were found in the bronchoalveolar lavage fluid (BALF) and sera of ozone- and CS-exposed mice. Furthermore, SP-D-knockout mice showed increased lipid-laden FMs and airway inflammation caused by ozone and CS exposure, similar to that exhibited by our study cohort of chronic smokers and COPD patients. We also showed that an exogenous recombinant fragment of human SP-D (rfhSP-D) prevented the formation of oxidized low-density lipoprotein (oxLDL)-induced FMs in vitro and reversed the airway inflammation and emphysematous changes caused by oxidative stress and CS exposure in vivo. SP-D upregulated bone marrow-derived macrophage (BMDM) expression of genes involved in countering the oxidative stress and lipid metabolism perturbations induced by CS and oxLDL. Our study demonstrates the crucial roles of SP-D in the lipid homeostasis of dysfunctional alveolar macrophages caused by ozone and CS exposure in experimental mouse emphysema, which may provide a novel opportunity for the clinical application of SP-D in patients with COPD.

关键词： Alveolar macrophages Chronic obstructive pulmonary diseases Surfactant protein D Lipid metabolism Ozone Cigarettes

Ascophyllum nodosum and Fucus vesiculosus ameliorate restenosis via improving inflammation and regulating the PTEN/PI3K/AKT signaling pathway

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Food Science and Human Wellness 2024年第3期13卷 1711-1728页

作者： Crystal Ngofi Zumbi Chun-Hsu Pan Hui-Yu Huang Chieh-hsi Wu Program in Clinical Drug Development from Herbal Medicine College of PharmacyTaipei Medical UniversityTaipei 11031China Program in Drug Discovery and Development Industry College of PharmacyTaipei Medical UniversityTaipei 11031China School of Pharmacy Taipei Medical UniversityTaipei 11031China Graduate Institute of Metabolism and Obesity Sciences Taipei Medical UniversityTaipei 11031China

Restenosis is a common complication following coronary angioplasty.The traditional use of seaweeds for health benefits has increasingly been explored,however few studies exist reporting its protective effects on the development of restenosis and gut dysbiosis.The aim of this study was to investigate the potential of seaweed extracts(SE) of Ascophyllum nodosum and Fucus vesiculosus in inhibiting intimal hyperplasia in a rat model of restenosis and its underlying mechanisms in macrophages and vascular smooth muscle cells(vSMCs).16S rRNA sequencing was done to investigate the regulatory effect of SE on the gut microbiome of injured rats.As indicated by the results,SE significantly inhibited the progression of intimal hyperplasia in vivo,attenuated inflammation in macrophages and could inhibit the proliferation,dedifferentiation and migration of vSMCs.It was observed through immunoblotting assays that treatment with SE significantly upregulated PTEN expression in macrophages and inhibited the upregulation of PI3K and AKT expression in vSMCs.Meanwhile,according to the 16S rRNA gene sequencing analysis,supplementation with SE modulated gut microbiota composition in injured rats.In conclusion,SE could ameliorate intimal hyperplasia by inhibiting inflammation and vSMCs proliferation through the regulation of the PTEN/PI3K/AKT pathway and modulating the gut microbiome.

关键词： Ascophyllum nodosum Fucus vesiculosus PTEN/PI3K/AKT Restenosis Macrophage Vascular smooth muscle cells Gut microbiota

Early-life EV-A71 infection augments allergen-induced airway inflammation in asthma through trained macrophage immunity

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Cellular & Molecular Immunology 2021年第2期18卷 472-483页

作者： Pei-Chi Chen Yu-Ting Shao miao-hsi hsieh Hui-Fang Kao Wen-Shuo Kuo Shih-Min Wang Shun-Hua Chen Lawrence Shih hsin Wu Hui-Ju Tsai Jiu-Yao Wang Institute of Basic Medical Sciences College of MedicineNational Cheng Kung UniversityTainanTaiwanChina Department of Microbiology and Immunology College of MedicineNational Cheng Kung UniversityTainanTaiwanChina Center for Allergy and Clinical Immunology Research College of MedicineNational Cheng Kung UniversityTainanTaiwanChina Department of Nursing National Tainan Junior College of NursingTainanTaiwanChina School of Chemistry and Materials Science Nanjing University of Information Science and TechnologyNanjingChina Department of Pediatrics National Cheng Kung University HospitalTainanTaiwanChina Graduate Institute of Biomedical Sciences China Medical UniversityTaichungTaiwanChina Division of Biostatistics and Bioinformatics Institute of Population Health SciencesNational Health Research InstitutesZhunanTaiwanChina Department of Pediatrics National Cheng Kung University HospitalNo139Sheng-Li RoadTainan 70428 TaiwanChina

Virus-induced asthma is prevalent among children,but its underlying mechanisms are unclear.Accumulated evidence indicates that early-life respiratory virus infection increases susceptibility to allergic asthma.Nonetheless,the relationship between systemic virus infections,such as enterovirus infection,and the ensuing effects on allergic asthma development is unknown.Early-life enterovirus infection was correlated with higher risks of allergic diseases in children.Adult mice exhibited exacerbated mite allergen-induced airway inflammation following recovery from EV-A71 infection in the neonatal period.Bone marrow-derived macrophages(BMDMs)from recovered EV-A71-infected mice showed sustained innate immune memory(trained immunity)that could drive naïve T helper cells toward Th2 and Th17 cell differentiation when in contact with mites.Adoptive transfer of EV-A71-trained BMDMs induced augmented allergic inflammation in naïve recipient mice,which was inhibited by 2-deoxy-D-glucose(2-DG)pretreatment,suggesting that trained macrophages following enterovirus infection are crucial in the progression of allergic asthma later in life.

关键词： trained immunity allergy asthma

Leptonic di-flavor and di-number violation processes at high energyμ^(±)μ^(±)colliders

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Chinese Physics C 2024年第4期48卷 34-50页

作者：杨金磊张肇西冯太傅 CAS Key Laboratory of Theoretical Physics Institute of Theoretical PhysicsChinese Academy of SciencesBeijing 100190China School of Physical Sciences University of Chinese Academy of SciencesBeijing 100049China School of Physical Science and Technology Lanzhou UniversityLanzhou 730000China Department of Physics Hebei UniversityKey Laboratory of High-precision Computation and Application of Quantum Field Theory of Hebei ProvinceBaoding 071002China

The leptonic di-flavor violation (LFV) processes μ^(±)μ^(±)→e^(±)e^(±) and μ^(±)μ^(±)→τ^(±)τ^(±) and leptonic di-number violation (LNV) processes μ^(±)μ^(±)→W_(i)^(±)W_(j)^(±) (i,j=1,2) at same-sign high energy μ^(±)μ^(±) colliders are studied. The new physics (NP) factors that may play roles in these processes are highlighted by cataloging them into three types. Taking into account the experimental constraints, the processes at μ^(±)μ^(±) colliders are computed, and the results are presented properly. The results lead to the conclusion that observing the NP factors through the LFV and LNV processes at TeV-energy μ^(±)μ^(±) colliders has significant advantages that cannot be achieved elsewhere. Therefore, once the techniques for muon acceleration and collision are developed successfully, the option of building same-sign high energy muon colliders should be seriously considered.

关键词： μ^(±)μ^(±)collider neutral lepton Majorana components

Molecular mechanism of therapeutic approaches for human gastric cancer stem cells

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World Journal of Stem Cells 2022年第1期14卷 76-91页

作者： hsi-Lung hsieh Ming-Chin Yu Li-Ching Cheng Ta-Sen Yeh Ming-Ming Tsai Department of Nursing Division of Basic Medical SciencesChang-Gung University of Science and TechnologyTaoyuan 333Taiwan Research Center for Chinese Herbal Medicine College of Human EcologyChang Gung University of Science and TechnologyTaoyuan 333Taiwan Department of Neurology Chang Gung Memorial HospitalTaoyuan 333Taiwan Department of General Surgery Chang Gung Memorial Hospital at LinkouTaoyuan 333Taiwan College of Medicine Chang Gung UniversityTaoyuan 333Taiwan Department of General Surgery New Taipei Municipal TuCheng HospitalNew Taipei 236Taiwan Department of General Surgery Chang Gung Memorial HospitalChiayi 613Taiwan

Gastric cancer(GC)is a primary cause of cancer-related mortality worldwide,and even after therapeutic gastrectomy,survival rates remain poor.The presence of gastric cancer stem cells(GCSCs)is thought to be the major reason for resistance to anticancer treatment(chemotherapy or radiotherapy),and for the development of tumor recurrence,epithelial–mesenchymal transition,and metastases.Additionally,GCSCs have the capacity for self-renewal,differentiation,and tumor initiation.They also synthesize antiapoptotic factors,demonstrate higher performance of drug efflux pumps,and display cell plasticity abilities.Moreover,the tumor microenvironment(TME;tumor niche)that surrounds GCSCs contains secreted growth factors and supports angiogenesis and is thus responsible for the maintenance of the growing tumor.However,the genesis of GCSCs is unclear and exploration of the source of GCSCs is essential.In this review,we provide up-todate information about GCSC-surface/intracellular markers and GCSC-mediated pathways and their role in tumor development.This information will support improved diagnosis,novel therapeutic approaches,and better prognosis using GCSC-targeting agents as a potentially effective treatment choice following surgical resection or in combination with chemotherapy and radiotherapy.To date,most anti-GCSC blockers when used alone have been reported as unsatisfactory anticancer agents.However,when used in combination with adjuvant therapy,treatment can improve.By providing insights into the molecular mechanisms of GCSCs associated with tumors in GC,the aim is to optimize anti-GCSCs molecular approaches for GC therapy in combination with chemotherapy,radiotherapy,or other adjuvant treatment.

关键词： Gastric cancer stem cells Stem cell-surface markers Tumor niche Tumor microenvironment

Quercetin exerts anti-inflammatory effects via inhibiting tumor necrosis factor-α-induced matrix metalloproteinase-9 expression in normal human gastric epithelial cells

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World Journal of Gastroenterology 2022年第11期28卷 1139-1158页

作者： hsi-Lung hsieh Ming-Chin Yu Li-Ching Cheng Mei-Yi Chu Tzu-Hao Huang Ta-Sen Yeh Ming-Ming Tsai Department of Nursing Division of Basic Medical SciencesChang-Gung University of Science and TechnologyTaoyuan 333TaiwanChina Research Center for Chinese Herbal Medicine College of Human EcologyChang Gung University of Science and TechnologyTaoyuan 333TaiwanChina Department of Neurology Chang Gung Memorial HospitalTaoyuan 333TaiwanChina Department of General Surgery New Taipei Municipal TuCheng HospitalNew Taipei 236TaiwanChina College of Medicine Chang Gung UniversityTaoyuan 333TaiwanChina Department of General Surgery Chang Gung Memorial HospitalTaoyuan 333TaiwanChina

BACKGROUND Gastric injury is the most common digestive system disease worldwide and involves inflammation,which can lead to gastric ulcer or gastric cancer(GC).Matrix metallopeptidase-9[MMP-9(gelatinase-B)]plays an important role in inflammation and GC progression.Quercetin and quercetin-rich diets represent potential food supplements and a source of medications for treating gastric injury given their anti-inflammatory activities.However,the effects and mechanisms of action of quercetin on human chronic gastritis and whether quercetin can relieve symptoms remain unclear.AIM To assess whether tumor necrosis factor-α(TNF-α)-induced MMP-9 expression mediates the anti-inflammatory effects of quercetin in normal human gastric mucosal epithelial cells.METHODS The normal human gastric mucosa epithelial cell line GES-1 was used to establish a normal human gastric epithelial cell model of TNF-α-induced MMP-9 protein overexpression to evaluate the antiinflammatory effects of quercetin.The cell counting Kit-8 assay was used to evaluate the effects of varying quercetin doses on cell viability in the normal GES-1 cell line.Cell migration was measured using Transwell assay.The expression of proto-oncogene tyrosine-protein kinase Src(cSrc),phospho(p)-c-Src,extracellular-signal-regulated kinase 2(ERK2),p-ERK1/2,c-Fos,p-c-Fos,nuclear factor kappa B(NF-κB/p65),and p-p65 and the effects of their inhibitors were examined using Western blot analysis and measurement of luciferase activity.p65 expression was detected by immunofluorescence.MMP-9 m RNA and protein levels were measured by quantitative reverse transcription polymerase chain reaction(q RT–PCR)and gelatin zymography,respectively.RESULTS q RT-PCR and gelatin zymography showed that TNF-αinduced MMP-9 m RNA and protein expression in a dose-and time-dependent manner.These effects were reduced by the pretreatment of GES-1 cells with quercetin or a TNF-αantagonist(TNFR inhibitor)in a dose-and timedependent manner.Quercetin and TNF-αantagonists decreased the TNF-α-induced phosphory

关键词： Anti-inflammatory Quercetin Matrix metallopeptidase-9 Tumor necrosis factor-α Normal human gastric epithelial cells

Design an Artificial Neural Network by MLP Method;Analysis of the Relationship between Demographic Variables, Resilience, COVID-19 and Burnout

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International Journal of Mental Health Promotion 2022年第6期24卷 825-841页

作者： Chao-hsi Huang Tsung-Shun hsieh hsiao-Ting Chien Ehsan Eftekhari-Zadeh Saba Amiri Office of Research and Development Tunghai UniversityTaichung407224TaiwanChina Nanyang Institute of Management The Central 059817Singapore Krirk University Thanon Ram IntraKhwaeng AnusawariKhet Bang KhenKrung Thep Maha Nakhon10220Thailand National Taiwan Normal University Graduate Institute of Information and Computer EducationTaipei10610TaiwanChina Institute of Optics and Quantum Electronics Friedrich Schiller University JenaJena07743Germany Managamenet and Entrepreneurship Department Razi UniversityKermanshah67146Iran

In addition to the effect that the COVID-19 pandemic has had on the physical and mental health of individuals,it has also led to a change in the mental and emotional state of many employees.Especially among businesses and private companies,which faced many restrictions due to the special conditions of the pandemic.Therefore,the present study aimed to design an artificial neural network with MLP technique to analyze the relationship between demographic variables,resilience,COVID-19 and burnout in start-ups in Iran.The research method was quantitative.Managers and employees of start-ups formed the statistical population of the study,based on the statistical sample size of the unlimited community,384 of them were tested.For data gathering,standard questionnaires include of MBI-GS and BRCS and researcher-made questionnaire of stress caused by COVID-19 were used.The validity of the questionnaires was confirmed by a panel of experts and their reliability was confirmed by Cronbach’s alpha coefficient.The number of neurons in the input layer was equal to 10,the number of neurons in the 1st hidden layer was equal to 7,the number of neurons in the output layer was equal to 1,and the number of epochs was equal to 500.70%of the data were used for training and 30%for testing.In the designed artificial neural network,all experiment data except one were correctly predicted and the obtained MAE error was less than 0.012%.Finally,he precision and correction of the presented model was confirmed by the obtained results.

关键词： Burnout artificial neural network multi-layer perceptron COVID-19 resilience

Tumor progression-dependent angiogenesis in gastric cancer and its potential application

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World Journal of Gastrointestinal Oncology 2019年第9期11卷 686-704页

作者： hsi-Lung hsieh Ming-Ming Tsai Research Center for Chinese Herbal Medicine College of Human EcologyChang Gung University of Science and TechnologyTaoyuan 333Taiwan Department of Nursing Division of Basic Medical SciencesChang-Gung University of Science and TechnologyTaoyuan 333Taiwan Department of Neurology Chang Gung Memorial HospitalTaoyuan 333Taiwan Department of General Surgery Chang Gung Memorial HospitalChiayi 613Taiwan

Despite improvements in the early diagnosis,prognosis and therapeutic strategies for gastric cancer(GC),human GC remains one of the most frequently diagnosed malignant tumors in the world,and the survival rate of GC patients remains very poor.Thus,a suitable therapeutic strategy for GC is important for prolonging survival.Both tumor cells themselves and the tumor microenvironment play an important role in tumorigenesis,including angiogenesis,inflammation,immunosuppression and metastasis.Importantly,these cells contribute to gastric carcinogenesis by altering the angiogenic phenotype switch.The development,relapse and spreading of tumors depend on new vessels that provide the nutrition,growth factors and oxygen required for continuous tumor growth.Therefore,a state of tumor dormancy could be induced by blocking tumor-associated angiogenesis.Recently,several antiangiogenic agents have been identified,and their potential for the clinical management of GC has been tested.Here,we provide an up-to-date summary of angiogenesis and the angiogenic factors associated with tumor progression in GC.We also review antiangiogenic agents with a focus on the anti-vascular endothelial growth factor receptor(VEGFR)-mediated pathway for endothelial cell growth and their angiogenesis ability in GC.However,most antiangiogenic agents have reported no benefit to overall survival(OS)compared to chemotherapy alone in local or advanced GC.In phase III clinical trials,only ramucirumab(anti-VEGFR blocker)and apatinib(VEGFR-TKI blocker)have reported an improved median overall response rate and prolonged OS and progression-free survival outcomes as a 2 nd-line agent combined with chemotherapy treatment in advanced GC.By providing insights into the molecular mechanisms of angiogenesis associated with tumor progression in GC,this review will hopefully aid the optimization of antiangiogenesis strategies for GC therapy in combination with chemotherapy and adjuvant treatment.

关键词： Gastric cancer Angiogenesis Vascular endothelial cell Angiogenic phenotype switch Anti-angiogenesis Tumor dormancy

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基于超分辨率的选区激光熔融熔池形貌研究

应用激光 2024年第4期44卷 28-37页

作者：吴磊孔令成傅盈西朱锟鹏中国科学院合肥物质科学研究院安徽合肥230031 中国科学技术大学研究生院科学岛分院安徽合肥230026 新加坡国立大学新国大苏州研究院江苏苏州215123

在选区激光熔融加工过程中,包含大量加工状态和工艺参数信息的熔池图像存在噪声污染、熔池边缘模糊等问题,因此提高熔池图像的分辨率对监测熔池状态具有重要意义。提出一种基于深度学习的熔池图像超分辨率重建算法,用于提取低分辨率熔... 详细信息

在选区激光熔融加工过程中,包含大量加工状态和工艺参数信息的熔池图像存在噪声污染、熔池边缘模糊等问题,因此提高熔池图像的分辨率对监测熔池状态具有重要意义。提出一种基于深度学习的熔池图像超分辨率重建算法,用于提取低分辨率熔池图像的浅层特征和深层特征并学习低分辨率图像到高分辨率图像之间的映射关系,使用亚像素卷积上采样完成熔池图像重建过程。分别对采集的高分辨率、退化后的低分辨率、重建的高分辨率熔池图像进行图像预处理和提取熔池形貌特征,以采集的高分辨率熔池图像的形貌特征为标签计算熔池特征误差率。结果显示,重建的熔池图像不仅可以提高分辨率,还大幅度降低了熔池形貌特征提取的误差率,为选区激光熔融成型过程监测和精准调控加工工艺参数提供了保证。

关键词：选区激光熔融熔池图像熔池形貌特征超分辨率重建