1.Application of fingertip photoplethysmogram assessment of endothelial function in screening coronary heart disease patients
Yunfei WANG ; Daoyuan SI ; Ping YANG
Journal of Jilin University(Medicine Edition) 2016;42(5):1014-1018
Objective:To investigate the application of photoplethysmogram in analyzing the fingertip pulse amplitude volume (PAV)to evaluate the endothelial function in diagnosing coronary heart disease,and to clarify its relationship with the risk factors of cardiovascular diseases.Methods:Total 409 patients with chest pain accepted coronary angiography (CAG)were selected and diveded into positive group (CAG+)(n=288)and negative group (CAG-) (n = 121)according to angiographic results.Fingertip photoplethysmogram was used to analyze the fingertip PAV by the way of applying endothelial function diagnostic after reactive ischemia,and the relationship between the PAV value and the risk factors of coronary heart diseases was analyzed,and the critical reference value of prediction index of coronary heart disease was determined.The risk factors such as age,gender,serum total cholesterol (TC ), low density lipoprotein (LDL ), high density lipoprotein (HDL ), non-HDL, serum triglyceride (TG),hypertension,diabetes,smoking,family history of coronary heart disease,body mass index (BMI)of the subjects in various groups were analyzed,and the relationship between the risk factors of coronary heart disease and PAV was analyzed by Logistic regression analysis.Results:The PAV of patients in CAG+group was significantly lower than that in CAG-group (P <0.01).The peak point of PAV was<1.37,if PAV<1.37 was used to predict the coronary heart disease,the predictive sensitivity,the specificity,the positive prediction and the negative prediction were 74.65%,44.63%, 76.24%, and 42.52%.The Logistic regression analysis showed that PAV was negatively associated with hypertension,smoking history,TG (OR= 1.476,OR=2.002, OR = 1.844;P < 0.01 ). Conclusion: PAV is associated with coronary heart disease and its risk factors (hypertension,smoking history,TG),and PAV=1.37 can be used as the peak point to predict the coronary heart disease.
2.Human ESC-derived vascular cells promote vascular regeneration in a HIF-1α dependent manner.
Jinghui LEI ; Xiaoyu JIANG ; Daoyuan HUANG ; Ying JING ; Shanshan YANG ; Lingling GENG ; Yupeng YAN ; Fangshuo ZHENG ; Fang CHENG ; Weiqi ZHANG ; Juan Carlos Izpisua BELMONTE ; Guang-Hui LIU ; Si WANG ; Jing QU
Protein & Cell 2024;15(1):36-51
Hypoxia-inducible factor (HIF-1α), a core transcription factor responding to changes in cellular oxygen levels, is closely associated with a wide range of physiological and pathological conditions. However, its differential impacts on vascular cell types and molecular programs modulating human vascular homeostasis and regeneration remain largely elusive. Here, we applied CRISPR/Cas9-mediated gene editing of human embryonic stem cells and directed differentiation to generate HIF-1α-deficient human vascular cells including vascular endothelial cells, vascular smooth muscle cells, and mesenchymal stem cells (MSCs), as a platform for discovering cell type-specific hypoxia-induced response mechanisms. Through comparative molecular profiling across cell types under normoxic and hypoxic conditions, we provide insight into the indispensable role of HIF-1α in the promotion of ischemic vascular regeneration. We found human MSCs to be the vascular cell type most susceptible to HIF-1α deficiency, and that transcriptional inactivation of ANKZF1, an effector of HIF-1α, impaired pro-angiogenic processes. Altogether, our findings deepen the understanding of HIF-1α in human angiogenesis and support further explorations of novel therapeutic strategies of vascular regeneration against ischemic damage.
Humans
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Vascular Endothelial Growth Factor A/metabolism*
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Endothelial Cells/metabolism*
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Transcription Factors/metabolism*
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Gene Expression Regulation
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Hypoxia/metabolism*
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Cell Hypoxia/physiology*
3.Single-nucleus profiling unveils a geroprotective role of the FOXO3 in primate skeletal muscle aging.
Ying JING ; Yuesheng ZUO ; Yang YU ; Liang SUN ; Zhengrong YU ; Shuai MA ; Qian ZHAO ; Guoqiang SUN ; Huifang HU ; Jingyi LI ; Daoyuan HUANG ; Lixiao LIU ; Jiaming LI ; Zijuan XIN ; Haoyan HUANG ; Juan Carlos Izpisua BELMONTE ; Weiqi ZHANG ; Si WANG ; Jing QU ; Guang-Hui LIU
Protein & Cell 2023;14(7):497-512
Age-dependent loss of skeletal muscle mass and function is a feature of sarcopenia, and increases the risk of many aging-related metabolic diseases. Here, we report phenotypic and single-nucleus transcriptomic analyses of non-human primate skeletal muscle aging. A higher transcriptional fluctuation was observed in myonuclei relative to other interstitial cell types, indicating a higher susceptibility of skeletal muscle fiber to aging. We found a downregulation of FOXO3 in aged primate skeletal muscle, and identified FOXO3 as a hub transcription factor maintaining skeletal muscle homeostasis. Through the establishment of a complementary experimental pipeline based on a human pluripotent stem cell-derived myotube model, we revealed that silence of FOXO3 accelerates human myotube senescence, whereas genetic activation of endogenous FOXO3 alleviates human myotube aging. Altogether, based on a combination of monkey skeletal muscle and human myotube aging research models, we unraveled the pivotal role of the FOXO3 in safeguarding primate skeletal muscle from aging, providing a comprehensive resource for the development of clinical diagnosis and targeted therapeutic interventions against human skeletal muscle aging and the onset of sarcopenia along with aging-related disorders.
Animals
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Humans
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Sarcopenia/metabolism*
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Forkhead Box Protein O3/metabolism*
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Muscle, Skeletal/metabolism*
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Aging/metabolism*
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Primates/metabolism*
4.FTO stabilizes MIS12 and counteracts senescence.
Sheng ZHANG ; Zeming WU ; Yue SHI ; Si WANG ; Jie REN ; Zihui YU ; Daoyuan HUANG ; Kaowen YAN ; Yifang HE ; Xiaoqian LIU ; Qianzhao JI ; Beibei LIU ; Zunpeng LIU ; Jing QU ; Guang-Hui LIU ; Weimin CI ; Xiaoqun WANG ; Weiqi ZHANG
Protein & Cell 2022;13(12):954-960
5.A single-nucleus transcriptomic atlas of primate testicular aging reveals exhaustion of the spermatogonial stem cell reservoir and loss of Sertoli cell homeostasis.
Daoyuan HUANG ; Yuesheng ZUO ; Chen ZHANG ; Guoqiang SUN ; Ying JING ; Jinghui LEI ; Shuai MA ; Shuhui SUN ; Huifen LU ; Yusheng CAI ; Weiqi ZHANG ; Fei GAO ; Andy PENG XIANG ; Juan Carlos Izpisua BELMONTE ; Guang-Hui LIU ; Jing QU ; Si WANG
Protein & Cell 2023;14(12):888-907
The testis is pivotal for male reproduction, and its progressive functional decline in aging is associated with infertility. However, the regulatory mechanism underlying primate testicular aging remains largely elusive. Here, we resolve the aging-related cellular and molecular alterations of primate testicular aging by establishing a single-nucleus transcriptomic atlas. Gene-expression patterns along the spermatogenesis trajectory revealed molecular programs associated with attrition of spermatogonial stem cell reservoir, disturbed meiosis and impaired spermiogenesis along the sequential continuum. Remarkably, Sertoli cell was identified as the cell type most susceptible to aging, given its deeply perturbed age-associated transcriptional profiles. Concomitantly, downregulation of the transcription factor Wilms' Tumor 1 (WT1), essential for Sertoli cell homeostasis, was associated with accelerated cellular senescence, disrupted tight junctions, and a compromised cell identity signature, which altogether may help create a hostile microenvironment for spermatogenesis. Collectively, our study depicts in-depth transcriptomic traits of non-human primate (NHP) testicular aging at single-cell resolution, providing potential diagnostic biomarkers and targets for therapeutic interventions against testicular aging and age-related male reproductive diseases.
Animals
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Male
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Testis
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Sertoli Cells/metabolism*
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Transcriptome
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Spermatogenesis/genetics*
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Primates
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Aging/genetics*
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Stem Cells