Background:Vascular smooth muscle cells(VSMCs)undergo a conversion from a contractile phenotype to a proliferative synthetic phenotype,contributing to the pathogenesis of cardiovascular diseases.Semaphorin 7A(SEMA7A)i...Background:Vascular smooth muscle cells(VSMCs)undergo a conversion from a contractile phenotype to a proliferative synthetic phenotype,contributing to the pathogenesis of cardiovascular diseases.Semaphorin 7A(SEMA7A)is a glycosylphosphatidylinositol-anchored membrane protein that plays an important role in vascular homeostasis by regulating endothelial cell behaviors.However,the expression and role of SEMA7A in VSMCs remain unclear.Methods:In this study,we screened for VSMC-regulating genes in publicly available datasets and analyzed the expression of SEMA7A in human coronary artery smooth muscle cells(hCASMCs)treated with platelet-derived growth factor-BB(PDGF-BB).The effects of SEMA7A overexpression and knockdown on hCASMC proliferation and migration were examined.The signaling pathways involved in the action of SEMA7A in hCASMCs were determined.Results:Bioinformatic analysis showed that SEMA7A was significantly dysregulated in VSMCs treated with oxidized low-density lipoprotein or overexpressing progerin,a pro-atherogenic gene.The PDGF-BB stimulation led to a concentration-and time-dependent induction of SEMA7A.Depletion of SEMA7A attenuated PDGF-BB-induced hCASMC proliferation and migration.Conversely,overexpression of SEMA7A enhanced hCASMC proliferation and migration.Mechanistically,SEMA7A stimulated the activation of theβ-catenin pathway and upregulated c-Myc,CCND1,and MMP7.Knockdown ofβ-catenin impaired SEMA7A-induced hCASMC proliferation and migration.Conclusions:SEMA7A triggers phenotype switching in VSMCs through theβ-catenin signaling pathway and may serve as a potential therapeutic target for cardiovascular diseases.展开更多
Change is the most fundamental property of a biomarker. In contrast to the blood, which is under homeostatic controls, urine reflects changes in the body earlier and is more sensitive, thus making it a better biomarke...Change is the most fundamental property of a biomarker. In contrast to the blood, which is under homeostatic controls, urine reflects changes in the body earlier and is more sensitive, thus making it a better biomarker source. Moreover, drawing blood from infants and toddlers is difficult and not tolerated well. For patients limited by language, communicating their chief complaint is difficult. Thus, monitoring biomarkers in urine can provide valuable clues for the diagnosis of diseases, especially pediatric diseases. Collecting urine from young children and some adult patients is more challenging than collecting it from healthy adults.Here, we propose a method that uses a fluff pulp diaper to collect urine. Urinary proteins are then eluted and adsorbed onto a piece of nitrocellulose membrane, which can be dried and stored in a vacuum bag. SDS-PAGE and LC-MS/MS analysis indicated that this method is reproducible, and similar proteins were identified as those obtained by an acetone precipitation method. With this simple and economical method, it is possible to collect and preserve urine samples from infants, toddlers, and patients with special needs, even for large-scale biomarker studies.展开更多
A biomarker is a measurable indicator associated with changes in physiological state or disease.In contrast to the blood which is under homeostatic controls,urine reflects changes in the body earlier and more sensitiv...A biomarker is a measurable indicator associated with changes in physiological state or disease.In contrast to the blood which is under homeostatic controls,urine reflects changes in the body earlier and more sensitively,and is therefore a better biomarker source.Lysine acetylation is an abundant and highly regulated post-translational modification.It plays a pivotal role in modulating diverse biological processes and is associated with various important diseases.Enrichment or visualization of proteins with specific post-translational modifications provides a method for sampling the urinary proteome and reducing sample complexity.In this study,we used anti-acetyllysine antibody-based immunoaffinity enrichment combined with high-resolution mass spectrometry to profile lysine-acetylated proteins in normal human urine.A total of 629 acetylation sites on 315 proteins were identified,including some very low-abundance proteins.This is the first proteome-wide characterization of lysine acetylation proteins in normal human urine.Our dataset provides a useful resource for the further discovery of lysine-acetylated proteins as biomarkers in urine.展开更多
Many patients with diabetes are not diagnosed at all or are diagnosed too late to be effectively treated, resulting in nonspecific symptoms and a long period of incubation of the disease. Pre-diabetes is an early warn...Many patients with diabetes are not diagnosed at all or are diagnosed too late to be effectively treated, resulting in nonspecific symptoms and a long period of incubation of the disease. Pre-diabetes is an early warning signal of diabetes, and the change of urine glucose in this period has been ignored even though urine has long been related with diabetes. In this study, Zucker diabetic fatty (ZDF) rats were used to test if there were changes in urine glucose before blood glucose increases. Six 8-week-old male ZDF rats (fa/fa) and Zucker lean (ZL) rats (fa/+) were fed with Purina 5008 high-fat diet and tested for fasting blood glucose and urine glucose. After 12 weeks of feeding, the urine glucose values of the ZL rats were normal (0–10 mmol L^(-1)), but the values of the ZDF model rats increased 10 weeks before their blood glucose levels elevated. The urine glucose values of the ZDF model rats showed a state of disorder that was frequently elevated (>10 mmol L^(-1)) and occasionally normal (0–10 mmol L^(-1)). This finding may provide an easy early screening for diabetes by long-term monitoring of urine glucose levels: pre-diabetes may be revealed by frequently disordered urine glucose levels over a period.展开更多
Dear Editor,Because urine is not under homeostatic control, changes occur earlier in urine than in blood; therefore, urine is a better source of early and sensitive biomarkers. The composition of urine is affected by ...Dear Editor,Because urine is not under homeostatic control, changes occur earlier in urine than in blood; therefore, urine is a better source of early and sensitive biomarkers. The composition of urine is affected by a variety of factors, and urine is susceptible to complex changes. To exclude the impact of multiple factors, an appropriate animal model can be used in which control over all experimental factors is possible and each factor can be separately observed. Additionally, some common confounding factors should be considered when choosing disease candidate biomarkers for clinical verification.展开更多
基金supported by the Basic Research Program of Shanxi Province(Free Exploration)of China(20210302124416)Science and Technology Grant for Selected Returned Chinese Scholars of Shanxi Province of China(20220043)Four“Batches”Innovation Project of Invigorating Medical through Science and Technology of Shanxi Province of China(2022XM08).
文摘Background:Vascular smooth muscle cells(VSMCs)undergo a conversion from a contractile phenotype to a proliferative synthetic phenotype,contributing to the pathogenesis of cardiovascular diseases.Semaphorin 7A(SEMA7A)is a glycosylphosphatidylinositol-anchored membrane protein that plays an important role in vascular homeostasis by regulating endothelial cell behaviors.However,the expression and role of SEMA7A in VSMCs remain unclear.Methods:In this study,we screened for VSMC-regulating genes in publicly available datasets and analyzed the expression of SEMA7A in human coronary artery smooth muscle cells(hCASMCs)treated with platelet-derived growth factor-BB(PDGF-BB).The effects of SEMA7A overexpression and knockdown on hCASMC proliferation and migration were examined.The signaling pathways involved in the action of SEMA7A in hCASMCs were determined.Results:Bioinformatic analysis showed that SEMA7A was significantly dysregulated in VSMCs treated with oxidized low-density lipoprotein or overexpressing progerin,a pro-atherogenic gene.The PDGF-BB stimulation led to a concentration-and time-dependent induction of SEMA7A.Depletion of SEMA7A attenuated PDGF-BB-induced hCASMC proliferation and migration.Conversely,overexpression of SEMA7A enhanced hCASMC proliferation and migration.Mechanistically,SEMA7A stimulated the activation of theβ-catenin pathway and upregulated c-Myc,CCND1,and MMP7.Knockdown ofβ-catenin impaired SEMA7A-induced hCASMC proliferation and migration.Conclusions:SEMA7A triggers phenotype switching in VSMCs through theβ-catenin signaling pathway and may serve as a potential therapeutic target for cardiovascular diseases.
基金supported by the National Natural Science Foundation of China(82100867,81941022,and 81530025)the Anhui Provincial Natural Science Foundation(2108085QH323)+3 种基金the China Postdoctoral Science Foundation(2021M693104)the National Key R&D Program of China(2021YFC2500500)the Strategic Priority Research Program of Chinese Academy of Sciences(XDB38010100)the Program for Innovative Research Team of The First Affiliated Hospital of USTC(CXGG02)。
基金supported by the National Key Research and Development Program of China(2016YFC1306300)the National Basic Research Program of China(2013CB530850)the Fundamental Research Funds for the Central Universities(11100704,10300-310421102)
文摘Change is the most fundamental property of a biomarker. In contrast to the blood, which is under homeostatic controls, urine reflects changes in the body earlier and is more sensitive, thus making it a better biomarker source. Moreover, drawing blood from infants and toddlers is difficult and not tolerated well. For patients limited by language, communicating their chief complaint is difficult. Thus, monitoring biomarkers in urine can provide valuable clues for the diagnosis of diseases, especially pediatric diseases. Collecting urine from young children and some adult patients is more challenging than collecting it from healthy adults.Here, we propose a method that uses a fluff pulp diaper to collect urine. Urinary proteins are then eluted and adsorbed onto a piece of nitrocellulose membrane, which can be dried and stored in a vacuum bag. SDS-PAGE and LC-MS/MS analysis indicated that this method is reproducible, and similar proteins were identified as those obtained by an acetone precipitation method. With this simple and economical method, it is possible to collect and preserve urine samples from infants, toddlers, and patients with special needs, even for large-scale biomarker studies.
基金supported by the National Key Research and Development Program of China(2018YFC0910202,2016YFC1306300)the Beijing Natural Science Foundation(7172076)+2 种基金the Beijing cooperative construction project(110651103)the Beijing Normal University(11100704)the Peking Union Medical College Hospital(2016-2.27)
文摘A biomarker is a measurable indicator associated with changes in physiological state or disease.In contrast to the blood which is under homeostatic controls,urine reflects changes in the body earlier and more sensitively,and is therefore a better biomarker source.Lysine acetylation is an abundant and highly regulated post-translational modification.It plays a pivotal role in modulating diverse biological processes and is associated with various important diseases.Enrichment or visualization of proteins with specific post-translational modifications provides a method for sampling the urinary proteome and reducing sample complexity.In this study,we used anti-acetyllysine antibody-based immunoaffinity enrichment combined with high-resolution mass spectrometry to profile lysine-acetylated proteins in normal human urine.A total of 629 acetylation sites on 315 proteins were identified,including some very low-abundance proteins.This is the first proteome-wide characterization of lysine acetylation proteins in normal human urine.Our dataset provides a useful resource for the further discovery of lysine-acetylated proteins as biomarkers in urine.
基金supported by the National Key R&D Program of China (2016YFC1306300)the National Basic Research Program of China (2013CB530805)+3 种基金the Beijing Natural Science Foundation (7173264, 7172076)the Fundamental Research Funds for the Central Universities (2015KJJCB21)the Beijing cooperative construction project(110651103)Beijing Normal University (11100704)
文摘Many patients with diabetes are not diagnosed at all or are diagnosed too late to be effectively treated, resulting in nonspecific symptoms and a long period of incubation of the disease. Pre-diabetes is an early warning signal of diabetes, and the change of urine glucose in this period has been ignored even though urine has long been related with diabetes. In this study, Zucker diabetic fatty (ZDF) rats were used to test if there were changes in urine glucose before blood glucose increases. Six 8-week-old male ZDF rats (fa/fa) and Zucker lean (ZL) rats (fa/+) were fed with Purina 5008 high-fat diet and tested for fasting blood glucose and urine glucose. After 12 weeks of feeding, the urine glucose values of the ZL rats were normal (0–10 mmol L^(-1)), but the values of the ZDF model rats increased 10 weeks before their blood glucose levels elevated. The urine glucose values of the ZDF model rats showed a state of disorder that was frequently elevated (>10 mmol L^(-1)) and occasionally normal (0–10 mmol L^(-1)). This finding may provide an easy early screening for diabetes by long-term monitoring of urine glucose levels: pre-diabetes may be revealed by frequently disordered urine glucose levels over a period.
文摘学习特别与单个分子、单个周转的规模的高空间与时间的分辨率，单个 nanocatalysts 的活动为催化机制并且设计有效催化剂的理解是必要的。几条途径被开发了在单个催化剂上监视催化反应。在这评论，我们总结了几条新分光镜、显微镜的途径的更新的进步，包括单个分子的荧光显微镜学，提高表面的拉曼光谱学，表面电浆子回声显微镜学和 X 光检查显微镜学，为单个分子、单个粒子的催化作用的学习。
基金supported by National Key Research and Development Program of China (2016 YFC 1306300)National Basic Research Program of China (2013CB530805)+3 种基金Beijing National Science Foundation (7173264, 7172076)the Fundamental Research Funds for the Central Universities (2015KJJCB21)Beijing Cooperative Construction Project (110651103)Beijing Normal University (11100704)
文摘Dear Editor,Because urine is not under homeostatic control, changes occur earlier in urine than in blood; therefore, urine is a better source of early and sensitive biomarkers. The composition of urine is affected by a variety of factors, and urine is susceptible to complex changes. To exclude the impact of multiple factors, an appropriate animal model can be used in which control over all experimental factors is possible and each factor can be separately observed. Additionally, some common confounding factors should be considered when choosing disease candidate biomarkers for clinical verification.
