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Iron metabolism and arthritis: Exploring connections and therapeutic avenues

中华医学杂志(英文版) 2024年第14期137卷 1651-1662页

作者： Zhuo Dachun Xiao Wenze Tang Yulong Jiang Shuai Geng Chengchun Xie Jiangnan Ma Xiaobei Zhang Qing Tang Kunhai Yu Yuexin Bai Lu Zou Hejian Liu Jing wang jiucun Department of Rheumatology Shanghai Pudong Hospital Human Phenome Institute Zhangjiang Fudan International Innovation Center Fudan University Shanghai China State Key Laboratory of Genetic Engineering School of Life Science Fudan University Shanghai China Department of Vascular Surgery Shanghai Pudong Hospital Shanghai Key Laboratory of Vascular Lesions Regulation and Remodeling Fudan University Pudong Medical Center Shanghai China Department of Anthropology and Human Genetics School of Life Sciences Ministry of Education Key Laboratory of Contemporary Anthropology Fudan University Shanghai China Division of Rheumatology Huashan Hospital State Key Laboratory of Genetic Engineering School of Life Science Fudan University Shanghai China Institute of Rheumatology Immunology and Allergy Allergy and Disease Research Center Fudan University Shanghai China Research Unit of Dissecting the Population Genetics and Developing New Technologies for Treatment and Prevention of Skin Phenotypes and Dermatological Diseases (2019RU058) Chinese Academy of Medical Sciences Beijing China

Iron is indispensable for the viablility of nearly all living organisms, and it is imperative for cells, tissues, and organisms to acquire this essential metal sufficiently and maintain its metabolic stability for survival. Disruption of iron homeostasis can lead to the development of various diseases. There is a robust connection between iron metabolism and infection, immunity, inflammation, and aging, suggesting that disorders in iron metabolism may contribute to the pathogenesis of arthritis. Numerous studies have focused on the significant role of iron metabolism in the development of arthritis and its potential for targeted drug therapy. Targeting iron metabolism offers a promising approach for individualized treatment of arthritis. Therefore, this review aimed to investigate the mechanisms by which the body maintains iron metabolism and the impacts of iron and iron metabolism disorders on arthritis. Furthermore, this review aimed to identify potential therapeutic targets and active substances related to iron metabolism, which could provide promising research directions in this field.

关键词： Iron metabolism Arthritis Inflammation Immunity Rheumatoid arthritis Psoriatic arthritis Gouty arthritis

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利用无创测量表征人体面部皮肤老化表型

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上海医药 2024年第11期45卷 42-45,66页

作者：刘一洲王久存马彦云复旦大学生命科学学院上海200438 复旦大学人类表型组研究院上海200438 中国医学科学院皮肤及皮肤病群体遗传学和防控新技术研究创新单元上海200438

目的:利用无创测量技术提取的中国人群面部皮肤理化参数建立表征皮肤老化表型的新指标。方法:招募100例不同年龄段的健康受试者,通过皮肤无创测试仪器检测皮肤含水量等皮肤参数,进行主成分分析(PCA)和广义线性模型分析(GLM)。结果:相关... 详细信息

目的:利用无创测量技术提取的中国人群面部皮肤理化参数建立表征皮肤老化表型的新指标。方法:招募100例不同年龄段的健康受试者,通过皮肤无创测试仪器检测皮肤含水量等皮肤参数,进行主成分分析(PCA)和广义线性模型分析(GLM)。结果:相关性分析发现胶原蛋白密度与年龄呈显著负相关(r=-0.31,P<0.01),眼角弹性指标R5(r=-0.612,P<0.0001)等参数明显随年龄增加而降低。广义线性模型建立的SAI与年龄关系更为显著(r=0.699,P<0.0001)。结论:面部皮肤老化主要表现为胶原蛋白流失,弹性降低,皮肤变黑变红,利用无创测量参数和广义线性模型建立的皮肤老化指数可以用来表征面部皮肤复杂的老化特征。

关键词：皮肤表型皮肤老化参数 PCA主成分分析广义线性模型无创测量

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LEPREL1是特发性肺纤维化的潜在治疗靶点

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复旦学报（自然科学版） 2024年第2期63卷 257-267,275,I0002页

作者：凡志婷唐宇龙陈雅慧孔祥贞杨婧漪王久存姜帅复旦大学生命科学学院上海200438 上海市浦东医院上海201200

为了寻找特发性肺纤维化(IPF)的潜在治疗靶点,从GEO获取IPF基因芯片数据,用R分析差异表达基因和通路;用STRING和Cytoscape筛选枢纽(HUB)基因;RNA-Seq和单细胞数据验证,肺纤维化小鼠实验验证,筛选具有相关性的基因,分析潜在通路。结果显... 详细信息

为了寻找特发性肺纤维化(IPF)的潜在治疗靶点,从GEO获取IPF基因芯片数据,用R分析差异表达基因和通路;用STRING和Cytoscape筛选枢纽(HUB)基因;RNA-Seq和单细胞数据验证,肺纤维化小鼠实验验证,筛选具有相关性的基因,分析潜在通路。结果显示:基因芯片数据集GSE10667、GSE53845、GSE48149共116例样本,差异基因132个,主要富集在细胞外基质、胶原等通路。STRING和Cytoscape筛选HUB基因,主要为COL1A1、CXCL12、LEPREL1等基因,其中LEPREL1表达显著下调(GSE10667,P_(adj)=0.00096;GSE53845,P_(adj)=0.0001048;GSE48149,P_(adj)=0.01517)。LEPREL1在RNA-Seq数据集GSE92592(P_(adj)=0.0288)、GSE83717(P_(adj)=0.006268)、GSE150910(P_(adj)=1.9528e-30)中均显著下调;在单细胞数据(GSE135893)中主要在AT2细胞中表达并有下调趋势;在肺纤维化小鼠的RT-qPCR和IHC中也表达显著下调。差异表达基因中有81个与LEPREL1具相关性的基因,主要与细胞黏附、钙离子、胶原形成、Wnt等通路相关。IPF的差异基因主要富集在胶原和细胞外基质通路,且AT2细胞中下调的LEPREL1可能是其潜在治疗靶点。

关键词：生物信息学特发性肺纤维化 LEPREL1

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高原青稞籽粒提取物的成分分析及其抗氧化活性研究

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上海医药 2024年第11期45卷 23-28,73页

作者：辜苗卢宝荣王久存马彦云内蒙古大学生命科学学院呼和浩特010021 复旦大学生命科学学院上海200433

目的:对比青稞籽粒的提取方法,以最大化获得其抗氧化活性物质。方法:采用生物发酵法、水提法、醇提法3种方法,对比分析青稞籽粒提取物中β-葡聚糖、总酚的提取效率。通过铁离子还原抗氧化能力测定(FRAP),2,2'-联氮-双-(3-乙基苯并噻唑啉... 详细信息

目的:对比青稞籽粒的提取方法,以最大化获得其抗氧化活性物质。方法:采用生物发酵法、水提法、醇提法3种方法,对比分析青稞籽粒提取物中β-葡聚糖、总酚的提取效率。通过铁离子还原抗氧化能力测定(FRAP),2,2'-联氮-双-(3-乙基苯并噻唑啉-6-磺酸)二铵盐(ABTS)、1,1-二苯基-2-三硝基苯肼(DPPH)自由基清除法检测青稞籽粒提取物的抗氧化能力。同时,利用高效液相色谱-串联质谱法(LC-MS/MS)对提取物进行代谢物鉴定。结果:醇提法表现出最优的提取效果,得到2.03µg/mLβ-葡聚糖和8.88µg/mL没食子酸当量的总酚,并在FRAP、ABTS、DPPH3种抗氧化能力检测法中都显示出最强的抗氧化能力。代谢物分析筛选出25种化合物,其中23种具有抗氧化活性。结论:本研究揭示了青稞籽粒提取物的代谢组成及其抗氧化活性,为深入理解青稞的营养特性及其潜在健康效益提供了科学依据,也为青稞在医药和保健品开发中的应用提供了理论支持。

关键词：高原青稞提取物抗氧化液相色谱-串联质谱法代谢组学

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紫外线B(UVB)损伤人皮肤基底膜屏障的分子特征

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上海医药 2024年第11期45卷 37-41,56页

作者：杨雅麟刘一洲王久存马彦云内蒙古大学生命科学学院呼和浩特010021 复旦大学生命科学学院上海200438

目的:观察UVB照射引起的基底膜屏障损伤的特征。方法:使用40 mJ/cm^(2)UVB照射HaCaT细胞,通过RNA-seq数据分析研究基底膜屏障相关基因的表达特征。通过透射电镜和免疫荧光染色,在3组离体皮肤组织中观察50 mJ/cm^(2)UVB连续照射3 d后基... 详细信息

目的:观察UVB照射引起的基底膜屏障损伤的特征。方法:使用40 mJ/cm^(2)UVB照射HaCaT细胞,通过RNA-seq数据分析研究基底膜屏障相关基因的表达特征。通过透射电镜和免疫荧光染色,在3组离体皮肤组织中观察50 mJ/cm^(2)UVB连续照射3 d后基底膜结构及关键屏障蛋白含量的变化。结果:发现了18个与基底膜相关的基因,其中17个基因表达下调,COL4A4、COL4A5、COL4A6、ITGB1、ITGA3、ITGA4、ITGA6、LAMA5的表达水平下调倍数超过1.5倍(P<0.05),而HPSE的表达上调了2.4倍(P<0.0001)。在离体皮肤组织实验中,UVB照射后观察到基底膜透明层和致密层断裂,半桥粒破坏,完整性和连续性受损,并且整合素蛋白含量下降(P<0.05)。结论:UVB照射会下调基底膜屏障结构相关基因的表达,上调乙酰肝素酶基因表达,造成基底膜结构紊乱以及基底膜关键屏障蛋白降解,使基底膜屏障受损。

关键词： UVB 离体皮肤组织培养皮肤基底膜损伤

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光的非视觉生物效应评价方法及其质量评估模型的构建

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照明工程学报 2024年第3期35卷 1-15页

作者：侯丹丹罗明郝洛西王久存林燕丹复旦大学信息科学与工程学院光源与照明工程系上海200433 复旦大学人类表型组研究院上海201203 复旦大学生命科学学院上海200433 浙江大学光电科学与工程学院浙江杭州310007 同济大学建筑与城市规划学院上海200082 复旦大学电光源研究所上海200433 复旦大学工程与应用技术研究院超越照明研究所上海200433

为提高光的非视觉生物效应研究方法选取提供科学依据,本研究采用文献分析法搜集筛选有效文献240篇对光的非视觉生物效应相关的认知/注意力水平、警觉度、情绪、睡眠质量、节律相位等5个人体指标的25种评价方法进行比较评估。研究结果:(1... 详细信息

为提高光的非视觉生物效应研究方法选取提供科学依据,本研究采用文献分析法搜集筛选有效文献240篇对光的非视觉生物效应相关的认知/注意力水平、警觉度、情绪、睡眠质量、节律相位等5个人体指标的25种评价方法进行比较评估。研究结果:(1)提出由“方法设计”、“心理学评价特征量”和“方法在光环境研究中适用性”三个维度的14个方法质量评估指标组成的方法质量评估模型;(2)构建适用于综合光环境研究的非视觉生物效应评价方法质量评估模型;(3)提出不同光环境特征量化分析方法。光的非视觉生物效应评价方法质量评估模型的建立可以为不同类型的光环境研究提供方法选取的依据和推荐,从而为光环境人因工程学研究的方法论提供理论基础。

关键词：非视觉生物效应认知水平睡眠质量信效度适用度

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Mitochondria as the Essence of Yang Qi in the Human Body

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Phenomics 2022年第5期2卷 336-348页

作者： Junjie Luo Shiwei Shen Jingjing Xia jiucun wang Zhenglong Gu Beijing Advanced Innovation Center for Food Nutrition and Human Health Key Laboratory of Precision Nutrition and Food QualityDepartment of Nutrition and HealthChina Agricultural UniversityBeijing 100193China State Key Laboratory of Genetic Engineering Collaborative Innovation Center for Genetics and Developmentand Human Phenome InstituteFudan UniversityShanghai 200438China Division of Nutritional Sciences Cornell UniversityIthacaNY 14853USA Greater Bay Area Institute of Precision Medicine(Guangzhou) School of Life SciencesFudan UniversityGuangzhou 511458China

The concept of Yang Qi in Traditional Chinese Medicine(TCM)has many similarities with mitochondria in modern *** are indispensable to human beings and closely related to life and *** article discusses the similarities in various aspects between mitochondria and Yang Qi,including body temperature,aging,newborns,circadian rhythm,immunity,and *** is well-known that Yang Qi is vital for human ***,decreased mitochondrial function is thought to be key to the development of various ***,we further explain diseases induced by Yang Qi deficiency,such as cancer,chronic fatigue syndrome,sleep disorder,senile dementia,and metabolic diseases,from the perspective of mitochondrial *** aim to establish similarities and connections between two important concepts,and hope our essay can stimulate further discussion and investigation on unifying important concepts in western medicine and alternative medicine,especially TCM,and provide unique holistic insights into understanding human health.

关键词： Mitochondria Yang Qi Diseases TCM(Traditional Chinese Medicine)

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nvolvement of collagen-binding heat shock protein 47 in scleroderma-associated fibrosis

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Protein & Cell 2015年第8期6卷 589-598页

作者： Haiyan Chu Ting Wu Wenyu Wu Wenzhen Tu Shuai Jiang Sidi Chen Yanyun Ma Qingmei Liu Xiaodong Zhoua Li Jin jiucun wang Ministry of Education Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering Collaborative Innovation Center for Genetics and Development School of Life Sciences and Institutes of Biomedica Sciences Fudan University Shanghai 200438 China Division of Dermatology Huashan Hospital Fudan University Shanghai 200040 China Division of Rheumatology Shanghai TCM-Integrated Hospital Shanghai 200082 China Division of Rheumatology University of Texas Health Science Center at Houston Houston TX 77030 USA Institute of Rheumatology Immunology and Allergy Fudan University Shanghai 20080 China

Uncontrolled fibrosis of skin and internal organs is the main characteristic of scleroderma, and collagen is a major extracellular matrix protein that deposits in the fibrotic organs. As the chaperone of collagen, heat shock protein 47 （HSP47） is closely related with the development of fbrosis. To explore the potential func- tion of HSP47 in the pathogenesis of scleroderma, the clinical, in vivo and in vitro studies were performed. In clinical, the increased mRNA level of HSP47 was observed in the skin fibroblasts and PBMC from scle- roderma patients, and the enhanced protein level of HSP47 was also detected in the skin biopsy and plasma of the above patients. Unexpectedly, the enhanced levels of HSP47 were positively correlated with the presence of anti-centromere antibody in scleroderma patients. Moreover, a high expression of HSP47 was found in the skin lesion of BLM-induced scleroderma mouse model. Further in vitro studies demonstrated that HSP47 knockdown could block the intracellular and extracellular collagen over-productions induced by exogenous TGF-13. Therefore, the results in this study provide direct evidence that HSP47 is involved in the pathogenesis of scleroderma. The high expression of HSP47 can be detected in the circulatory system of scleroderma patients, indicating that HSP47 maybecome a pathological marker to assess the progres- sion of scleroderma, and also explain the systemic fibrosis of scleroderma. Meanwhile, collagen over-ex- pression is blocked by HSP47 knockdown, suggesting the possibility that HSP47 can be a potential therapeutic target for scleroderma.

关键词： systemic sclerosis fibrosis collagenheat shock protein 47 anti-centromere antibody,therapeutic target

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Skin Microbiome,Metabolome and Skin Phenome,from the Perspectives of Skin as an Ecosystem

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Phenomics 2022年第6期2卷 363-382页

作者： Huizhen Chen Qi Zhao Qian Zhong Cheng Duan Jean Krutmann jiucun wang Jingjing Xia Human Phenome Institute School of Life SciencesFudan UniversityShanghai 200438China Department of Epidemiology School of Public HealthCheeloo College of MedicineShandong UniversityJinan 250012China IUF-Leibniz Research Institute for Environmental Medicine Dusseldorf D-40225Germany Greater Bay Area Institute of Precision Medicine(Guangzhou) School of Life SciencesFudan UniversityGuangzhou 511458China Research Unit of Dissecting the Population Genetics and Developing New Technologies for Treatment and Prevention of Skin Phenotypes and Dermatological Diseases(2019RU058) Chinese Academy of Medical SciencesShanghai 200438China

Skin is a complex ecosystem colonized by millions of microorganisms,including bacteria,fungi,and *** microbiota is believed to exert critical functions in maintaining host skin *** the structure of skin microbial community is the first step to overview the ***,the community composition is highly individualized and extremely *** explore the fundamental factors driving the complexity of the ecosystem,namely the selection pressures,we review the present studies on skin microbiome from the perspectives of *** review summarizes the following:(1)the composition of substances/nutrients in the cutaneous ecological environment that are derived from the host and the environment,highlighting their proposed function on skin microbiota;(2)the features of dominant skin commensals to occupy ecological niches,through self-adaptation and microbe–microbe interactions;(3)how skin microbes,by their structures or bioactive molecules,reshape host skin phenotypes,including skin immunity,maintenance of skin physiology such as pH and hydration,ultraviolet(UV)protection,odor production,and wound *** review aims to re-examine the host–microbe interactions from the ecological perspectives and hopefully to give new inspiration to this field.

关键词： Skin microbiome Metabolome Phenome Microbe–microbe interactions Ecological niches

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Presence of Rare Variants is Associated with Poorer Survival in Chinese Patients with Amyotrophic Lateral Sclerosis

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Phenomics 2023年第2期3卷 167-181页

作者： Siqi Dong Xianhong Yin Kun wang Wenbo Yang Jiatong Li Yi wang Yanni Zhou Xiaoni Liu jiucun wang Xiangjun Chen Department of Neurology Huashan Hospital and Institute of NeurologyFudan UniversityShanghai 200040China National Center for Neurological Disorders Shanghai 200040China Department of Anthropology and Human Genetics School of Life SciencesFudan UniversityShanghai 200438China Human Phenome Institute Fudan UniversityShanghai 200433China

Amyotrophic lateral sclerosis(ALS)is a fatal neurodegenerative disorder with phenotypic and genetic *** studies have suggested an oligogenic basis of ALS,in which the co-occurrence of two or more genetic variants has additive or synergistic deleterious *** assess the contribution of possible oligogenic inheritance,we profiled a panel of 43 relevant genes in 57 sporadic ALS(sALS)patients and eight familial ALS(fALS)patients from five pedigrees in east *** filtered rare variants using the combination of the Exome Aggregation Consortium,the 1000 Genomes and the HuaBiao *** analyzed patients with multiple rare variants in 43 known ALS causative genes and the genotype–phenotype ***,we detected 30 rare variants in 16 different genes and found that 16 of the sALS patients and all the fALS patients examined harbored at least one variant in the investigated genes,among which two sALS and four fALS patients harbored two or more *** note,the sALS patients with one or more variants in ALS genes had worse survival than the patients with no ***,in one fALS pedigree with three variants,the family member with three variants(Superoxide dismutase 1(SOD1)p.V48A,Optineurin(OPTN)p.A433V and TANK binding kinase 1(TBK1)p.R573H)exhibited much more severe disease phenotype than the member carrying one variant(TBK1 p.R573H).Our findings suggest that rare variants could exert a negative prognostic effect,thereby supporting the oligogenic inheritance of ALS.

关键词： Amyotrophic lateral sclerosis Oligogenic inheritance Survival Superoxide dismutase 1 TANK-binding kinase 1 Optineurin

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