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Laccase/caffeic acid-catalyzed crosslinking coupled with galactomannan alters the conformational structure of ovalbumin and alleviates Th2-mediated allergic asthma

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Food Science and Human Wellness 2024年第4期13卷 1962-1973页

作者： Ishfaq Ahmed Suidong Ouyang Shengquan Wu Haochang Song Miaoyuan Zhang Renxing Luo Peishan Lu Jiaqi Deng Tingting Zheng Yanyan Wang Xinguang Liu gonghua huang Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguan 523808China Haide College Ocean University of ChinaLaoshan CampusQingdao 266100China School of Medical Technology Guangdong Medical UniversityDongguan 523808China

Ovalbumin(OVA)is the major allergenic protein that can induce T helper 2(Th2)-allergic reactions,for which current treatment options are inadequate.In this study,we developed a polymerized hypoallergenic OVA product via laccase/caffeic acid(Lac/CA)-catalyzed crosslinking in conjunction with galactomannan(Man).The formation of high molecular weight crosslinked polymers and the Ig G-binding were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis(SDS-PAGE)and Western blotting.The study indicated that Lac/CA-catalyzed crosslinking plus Man conjugation substantially altered secondary and tertiary structures of OVA along with the variation in surface hydrophobicity.Gastrointestinal digestion stability assay indicated that crosslinked OVA exhibited less resistance in simulated gastric fluid(SGF)and simulated intestinal fluid(SIF).Mouse model study indicated that Lac-Man/OVA ameliorated eosinophilic airway inflammatory response and efficiently downregulated the expression of Th2-related cytokines(interleukin(IL)-4,IL-5,and IL-13),and upregulated IFN-γand IL-10 expression.Stimulation of bone marrow-derived dendritic cells with Lac-Man/OVA suppressed the expression of phenotypic maturation markers(CD80 and CD86)and MHC class II molecules,and suppressed the expression levels of proinflammatory cytokines.The knowledge obtained in the present study offers an effective way to acquire a hypoallergenic OVA product that can have a therapeutic effect in alleviating OVA-induced allergic asthma.

关键词： Ovalbumin Laccase Galactomannan Conformational structure Asthma

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The kinase p38αfunctions in dendritic cells to regulate Th2-cell differentiation and allergic inflammation

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Cellular & Molecular Immunology 2022年第7期19卷 805-819页

作者： Miaomiao Han Jingyu Ma Suidong Ouyang Yanyan Wang Tingting Zheng Peishan Lu Zihan Zheng Weiheng Zhao Hongjin Li Yun Wu Baohua Zhang Ran Hu Kinya Otsu Xinguang Liu Ying Wan Huabin Li gonghua huang ENT Institute and Department of Otorhinolaryngology Eye&ENT HospitalFudan University200031 ShanghaiChina Shanghai Institute of Immunology Shanghai Jiao Tong University School of Medicine200025 ShanghaiChina Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics Guangdong Medical University523808 DongguanChina Biomedical Analysis Center Army Medical University400038 ChongqingChina Department of Cardiovascular Medicine Graduate School of MedicineOsaka UniversityOsaka 565-0871Japan School of Cardiovascular Medicine and Sciences King’s College LondonLondon SE59NUUK Present address:Tongji Hospital Tongji Medical CollegeHuazhong University of Science and Technology430030 WuhanChina Department of Dermatology Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese Medicine200437 ShanghaiChina Department of Clinical Laboratory Medicine Shanghai Tenth People’s Hospital of Tongji University200072 ShanghaiChina Present address:Basic Department of Cancer Center Shanghai Tenth People’s Hospital of Tongji University200072 ShanghaiChina

Dendritic cells(DCs)play a critical role in controlling T helper 2(Th2)cell-dependent diseases,but the signaling mechanism that triggers this function is not fully understood.We showed that p38αactivity in DCs was decreased upon HDM stimulation and dynamically regulated by both extrinsic signals and Th2-instructive cytokines.p38α-specific deletion in cDC1s but not in cDC2s or macrophages promoted Th2 responses under HDM stimulation.Further study showed that p38αin cDC1s regulated Th2-cell differentiation by modulating the MK2−c-FOS−IL-12 axis.Importantly,crosstalk between p38α-dependent DCs and Th2 cells occurred during the sensitization phase,not the effector phase,and was conserved between mice and humans.Our results identify p38αsignaling as a central pathway in DCs that integrates allergic and parasitic instructive signals with Th2-instructive cytokines from the microenvironment to regulate Th2-cell differentiation and function,and this finding may offer a novel strategy for the treatment of allergic diseases and parasitic infection.

关键词： Allergy p38α dendritic cell Th2

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Laccase/caffeic acid-catalyzed crosslinking coupled with galactomannan alters the conformational structure of OVA and alleviates Th2-mediated allergic asthma

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Food Science and Human Wellness 2023年

作者： Ishfaq Ahmed Suidong Ouyang Shengquan Wu Haochang Song Miaoyuan Zhang Renxing Luo Peishan Lu Jiaqi Deng Tingting Zheng Yanyan Wang Xinguang Liu gonghua huang School of Medical Technology Guangdong Medical University Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics The First Dongguan Affiliated Hospital Guangdong Medical University Haide College Ocean University of China

Ovalbumin (OVA) is the major allergenic protein that can induce T helper 2 (Th2)-allergic reactions for which current treatment options are inadequate. In this study， we developed a polymerized hypoallergenic OVA product via laccase/caffeic acid (Lac/CA)-catalyzed crosslinking in conjunction with galactomannan (Man). The formation of high molecular weight crosslinked polymers and the IgG-binding were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting. The study indicated that Lac/CA-catalyzed crosslinking plus Man conjugation substantially altered secondary and tertiary structures of OVA along with the variation in surface hydrophobicity. Gastrointestinal digestion stability assay indicated that crosslinked OVA exhibited less resistance in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). Mouse model study indicated that Lac-Man/OVA ameliorated eosinophilic airway inflammatory response and efficiently downregulated the expression of Th2-related cytokines (IL-4， IL-5， and IL-13)， and upregulated IFN-γ and IL-10 expression. Stimulation of bone marrow-derived dendritic cells with Lac-Man/OVA suppressed the expression of phenotypic maturation markers (CD80， and CD86) and MHC class II molecules， and suppressed the expression levels of proinflammatory cytokines. The knowledge obtained in the present study offers an effective way to acquire a hypoallergenic OVA product that can have a therapeutic effect in alleviating OVA-induced allergic asthma.

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Regulation of TH17 cell differentiation by innate immune signals

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Cellular & Molecular Immunology 2012年第4期9卷 287-295页

作者： gonghua huang Yanyan Wang Hongbo Chi Department of Immunology St Jude Children's Research Hospital Memphis TN USA

Upon antigen stimulation, naive T helper cells differentiate into distinct lineages to attain specialized properties and effector functions. TH17 cells, a recently identified lineage of CD4＋ effector T cells, play a key role in the immune defense against fungi and extracellular bacteria, but also contribute to the pathogenesis of many autoimmune conditions. The differentiation of TH 17 cells is orchestrated by an intricate network of signaling pathways and transcriptional regulators in T cells. While the involvement of T cell-intrinsic pathways has been described extensively, we are just beginning to appreciate how TH17 cell development is shaped by extrinsic pathways, espec- ially the innate immune signals. Dendritic cells （DCs）, the most important cell type to bridge innate and adaptive immunity, drive TH17 cell differentiation by providing antigenic, costimulatory and cytokine signals. This is mediated by the recognition of innate and inflam- matory signals by DCs via pattern recognition receptors, cytokine receptors and other immunomodulatory receptors that in turn activate the intracellular signaling network. In particular, p38a MAP kinase has emerged as a critical pathway to program DC-dependent TH17 cell differentiation by integrating multiple instructive signals in DCs. Here, we summarize the current knowledge on the mechanisms by which DC-derived innate immune signals drive TH17 cell differentiation.

关键词： dendritic cells innate immunity MAPK T-cell differentiation TH17 cells

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Comparison of toxicity between lanthanum oxide nanoparticles and lanthanum chloride

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Journal of Rare Earths 2024年第2期42卷 424-430,I0007页

作者： Kun huang Songchang Lai Miao Guo Xingwu Zhu Jiashuangwei Yuan Zhehao Liu gonghua Hu Yanfang Gao School of Public Health and Health Management Gannan Medical UniversityGanzhou341000China

Due to the wide application of rare earth elements,lanthanum(La) is gradually accumulated in our living environment.Lanthanum can enter the body through a variety of routes,which has a series of effects on various systems.As a consequence,the safety of lanthanum deserves our attention.This study aims to compare the toxicity of lanthanum oxide nanoparticles(La_(2)O_(3) NPs) and lanthanum chloride(LaCl_(3)) and enrich the toxicity evaluation of lanthanum.Therefore,a 30 d intragastal experiment was conducted.C57BL/6j mice were given by La_(2)O_(3) NPs solution and LaCl_(3) solution respectively at doses of 0,30,60 and120 mg/kg BW(lanthanum content).The results show that,compared with the control group,both La_(2)O_(3)NPs and LaCl_(3) can reduce the body weight of female mice in the high-dose group,but for male mice,the high-dose La_(2)O_(3) NPs solution can increase the body weight,while LaCl_(3) has the opposite effect.The coefficients of liver,kidney,heart,lung,uterine and ovaries increase first and then decrease with the exposure dose,but testes and epididymides coefficient keep increasing with the exposure of LaCl_(3) and La_(2)O_(3) NPs.La_(2)O_(3) NPs and LaCl_(3) can reduce the concentration of triglycerides(TG) and increase the level of low density lipoprotein(LDL),but the effect of La_(2)O_(3) NPs is more obvious.La_(2)O_(3) NPs and LaCl_(3) can reduce the concentration of malondialdehyde(MDA),increase the total antioxidant capacity(T-AOC)and enhance the activity of catalase(CAT),but LaCl_(3) has more obvious protective effects on oxidative stress.La_(2)O_(3) NPs and LaCl_(3) have potential risks to liver,and the toxicity of La_(2)O_(3) NPs might be higher than that of LaCl_(3).

关键词： Rare earth elements Lanthanum oxide nanoparticles Lanthanum chloride Lipid metabolism Oxidative stress

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MKP-1在结核分枝杆菌感染中的作用和研究进展

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微生物学报 2017年第7期57卷 978-984页

作者：黄丽军黄功华刘新光广东医科大学衰老研究所广东东莞523808 广东医科大学广东省医学分子诊断重点实验室广东东莞523808 广东医科大学附属深圳第三医院广东深圳518020 上海交通大学医学院上海市免疫学研究所上海200025

有丝分裂原激活的蛋白激酶(Mitogen-Activated Protein Kinase,MAPK)信号通路是细胞感知外源性刺激并作出有效免疫应答的最重要的细胞内信号通路之一。近年来的研究表明:MAPK的表达异常与结核病的发生、发展密切相关。MAPK磷酸酶(MAPK p... 详细信息

有丝分裂原激活的蛋白激酶(Mitogen-Activated Protein Kinase,MAPK)信号通路是细胞感知外源性刺激并作出有效免疫应答的最重要的细胞内信号通路之一。近年来的研究表明:MAPK的表达异常与结核病的发生、发展密切相关。MAPK磷酸酶(MAPK phosphatases,MKPs)是一类在细胞内水解MAPKs家族的磷酸酶,通过负向调控MAPKs的活性,从而在调节细胞的应激、分化、增殖、凋亡等过程中发挥重要的作用,其中MKP-1是MKPs家族中被报道最多的成员,具有最强的去磷酸化能力。本文综述了MKP-1在结核分枝杆菌感染中的作用和研究进展。

关键词：有丝分裂原激活的蛋白激酶有丝分裂原激活的蛋白激酶磷酸酶1 结核病

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探讨无创颅内压监测对颅脑外伤的临床应用

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中外医学研究 2018年第2期16卷 125-127页

作者：黄龚华启东市人民医院江苏启东226200

目的:研究分析无创颅内压监测对颅脑外伤的临床应用价值。方法:在笔者所在医院接收的颅脑外伤患者中,随机选取56例作为研究对象,所有研究对象均于2015年1月-2016年12月入院治疗。按照颅内压监测结果的不同,将患者分为甲、乙、丙、丁组,... 详细信息

目的:研究分析无创颅内压监测对颅脑外伤的临床应用价值。方法:在笔者所在医院接收的颅脑外伤患者中,随机选取56例作为研究对象,所有研究对象均于2015年1月-2016年12月入院治疗。按照颅内压监测结果的不同,将患者分为甲、乙、丙、丁组,所有患者均进行无创颅内压监测。对患者颅内压监测情况进行观察、记录,并分析无创颅内压监测技术应用价值。结果:甲组、乙组的预后良好率均优于丁组,差异均有统计学意义(χ~2=8.040 5、7.304 4,P0.05)。结论:无创颅内压监测对颅脑外伤的临床应用价值较高,能为判断患者病情、制定治疗方案、判断患者预后情况提供科学依据,值得推广应用。

关键词：无创颅内压监测颅脑外伤应用价值

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DC介导的Th2细胞免疫紊乱在Th2细胞免疫紊乱相关过敏性疾病中的研究进展

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医学综述 2021年第10期27卷 1873-1879页

作者：王斌黄功华刘新光广东省医学分子诊断重点实验室广东医科大学衰老研究所广东医科大学生物化学与分子生物学研究所广东东莞523808

辅助性T细胞2(Th2细胞)是体液免疫的重要组成部分,其通过分泌白细胞介素(IL)-4、IL-5、IL-13等细胞因子参与2型免疫反应。树突状细胞(DC)是主要的抗原呈递细胞,其通过分泌CC趋化因子配体(CCL) 17、CCL22等趋化因子,摄取、加工、处理变应... 详细信息

辅助性T细胞2(Th2细胞)是体液免疫的重要组成部分,其通过分泌白细胞介素(IL)-4、IL-5、IL-13等细胞因子参与2型免疫反应。树突状细胞(DC)是主要的抗原呈递细胞,其通过分泌CC趋化因子配体(CCL) 17、CCL22等趋化因子,摄取、加工、处理变应原,并上调自身表面共刺激分子。随后,DC将抗原肽呈递给初始T细胞并使其进一步分化为Th2细胞。特应性皮炎、变应性哮喘和食物过敏是DC介导的Th2免疫紊乱相关过敏性疾病,近年来针对这些疾病的发病机制研究已取得一定进展。为研发出更加个性化和靶向性的药物,未来DC的异质性及在不同器官中的功能差异仍需进一步研究。

关键词：特应性皮炎变应性哮喘食物过敏树突状细胞辅助性T细胞2 免疫紊乱

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炎症性肠病的免疫调控研究进展

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医学综述 2019年第11期25卷 2081-2085,2091页

作者：陈策黄功华刘新光广东医科大学衰老研究所广东省医学分子诊断重点实验室广东医科大学广东东莞523808 广东医科大学生物化学与分子学研究所广东东莞523808 上海市免疫学研究所上海交通大学医学院上海200025

炎症性肠病(IBD)是一类高发、病因尚未明确的慢性自身免疫性疾病,在全世界范围内发病率呈上升趋势。肠道微环境稳态失衡、免疫功能失调、环境变化或遗传因素都可能导致疾病的发生。免疫细胞,如巨噬细胞、树突状细胞、固有淋巴细胞以及T... 详细信息

炎症性肠病(IBD)是一类高发、病因尚未明确的慢性自身免疫性疾病,在全世界范围内发病率呈上升趋势。肠道微环境稳态失衡、免疫功能失调、环境变化或遗传因素都可能导致疾病的发生。免疫细胞,如巨噬细胞、树突状细胞、固有淋巴细胞以及T细胞、B细胞在IBD中发挥重要作用。巨噬细胞或树突状细胞通过上调炎症细胞因子表达,T细胞、B细胞通过分泌细胞因子或抗体参与IBD免疫调控。阐明IBD免疫作用的机制,可能为IBD的治疗提供新靶点。

关键词：炎症性肠病巨噬细胞树突状细胞 T细胞 B细胞

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基于5G MEC的配网多端差动保护稳态精度校验方法

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微型电脑应用 2024年第1期40卷 69-72页

作者：陈端云苏素燕陈锦山谢石木林黄见虹侯功华国网福建省电力有限公司福建福州350001 国网福建省电力有限公司电力科学研究院福建福州350007 国网信通亿力科技有限责任公司福建福州350003 国网福建省电力有限公司福州供电公司福建福州350009

为了提高配网多端差动保护的检测精度,减少延迟,提出基于5G MEC的配网多端差动保护稳态精度校验方法。该方法以5G核心网多模块化的网络功能架构完成集中管控运营,结合MEC平台实现本地分流;将线路划分成多个多端差动保护区域,通过多种协... 详细信息

为了提高配网多端差动保护的检测精度,减少延迟,提出基于5G MEC的配网多端差动保护稳态精度校验方法。该方法以5G核心网多模块化的网络功能架构完成集中管控运营,结合MEC平台实现本地分流;将线路划分成多个多端差动保护区域,通过多种协议完成差动保护的多端通信;获取平衡系数消除不平衡差流,利用相位补偿简化的电流转化手段得到差动电流,完成配网多端差动保护稳态精度的校验。实验结果表明,所提方法传输延时低于88μs,校验后的差动保护动作灵敏度明显提升,动作率为100%,可提高配网多端差动保护稳态精度。

关键词： 5G MEC 配网多端差动保护稳态精度校验相位补偿

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