High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and neuroscience.High-mobility group box 1 in the ex...High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and neuroscience.High-mobility group box 1 in the extracellular space functions as a pro-inflammatory damage-associated molecular pattern,which has been proven to play an important role in a wide variety of central nervous system disorders such as ischemic stroke,Alzheimer’s disease,frontotemporal dementia,Parkinson’s disease,multiple sclerosis,epilepsy,and traumatic brain injury.Several drugs that inhibit high-mobility group box 1 as a damage-associated molecular pattern,such as glycyrrhizin,ethyl pyruvate,and neutralizing anti-high-mobility group box 1 antibodies,are commonly used to target high-mobility group box 1 activity in central nervous system disorders.Although it is commonly known for its detrimental inflammatory effect,high-mobility group box 1 has also been shown to have beneficial pro-regenerative roles in central nervous system disorders.In this narrative review,we provide a brief summary of the history of high-mobility group box 1 research and its characterization as a damage-associated molecular pattern,its downstream receptors,and intracellular signaling pathways,how high-mobility group box 1 exerts the repair-favoring roles in general and in the central nervous system,and clues on how to differentiate the pro-regenerative from the pro-inflammatory role.Research targeting high-mobility group box 1 in the central nervous system may benefit from differentiating between the two functions rather than overall suppression of high-mobility group box 1.展开更多
背景:既往研究表明,中老年人体内组织蛋白酶K水平可通过影响骨密度来干预骨质疏松的发生和发展,但组织蛋白酶家族与其他人群骨密度之间是否存在因果关系仍未知。目的:探讨组织蛋白酶与骨密度的因果关系。方法:从IEU Open GWAS数据库提取...背景:既往研究表明,中老年人体内组织蛋白酶K水平可通过影响骨密度来干预骨质疏松的发生和发展,但组织蛋白酶家族与其他人群骨密度之间是否存在因果关系仍未知。目的:探讨组织蛋白酶与骨密度的因果关系。方法:从IEU Open GWAS数据库提取与8种组织蛋白酶相关的遗传位点作为工具变量,以5个年龄段人群的骨密度作为结局。通过双向孟德尔随机化分析,评估组织蛋白酶与骨密度的因果关系。使用Cochran’s Q检验评估遗传工具变量的异质性,使用MR-Egger截距检验评估多效性,使用留一法评估作为工具变量的单核苷酸多态性对暴露和结局因果关系影响的敏感性。结果与结论:①正向孟德尔随机化的逆方差加权法结果显示,组织蛋白酶H与>45岁且≤60岁人群的骨密度呈负相关[OR(95%CI)=0.965(0.94-0.99),P=0.04],组织蛋白酶Z与>30岁且≤45岁人群的骨密度呈负相关[OR(95%CI)=1.06(1.00-1.11),P=0.03];②敏感性分析结果显示因果关系稳定,MR-Egger截距分析未检测到潜在的水平多效性;③反向孟德尔随机化结果显示,骨密度对组织蛋白酶无显著反向作用;④上述结果证实,组织蛋白酶对部分年龄段人群骨密度会造成影响,可能会增加骨质疏松症的发病风险,应给予更多关注。展开更多
In his verses, a poet lauded Xiangquan Liquor as "A bibber had a few cups of Xiangquan Liquor, and he became intoxicated for three thousand years. When he sobered up and took his cup again, the bibber became a ce...In his verses, a poet lauded Xiangquan Liquor as "A bibber had a few cups of Xiangquan Liquor, and he became intoxicated for three thousand years. When he sobered up and took his cup again, the bibber became a celestial of wine." The Xiangquan Liquor produced by Hunan Xiangquan Group boasts a unique bouquet distinguishing it in flavour from other name brand spirits on the domestic market. The type of its bouquet, a compound one, is展开更多
基金supported by a grant of the M.D.-Ph.D./Medical Scientist Training Program through the Korea Health Industry Development Institute(KHIDI)funded by the Ministry of Health&Welfare,Republic of Korea(to HK)+3 种基金supported by National Research Foundation of Korea(NRF)grants funded by the Korean government(MSITMinistry of Science and ICT)(NRF2019R1A5A2026045 and NRF-2021R1F1A1061819)a grant from the Korean Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI),funded by the Ministry of Health&Welfare,Republic of Korea(HR21C1003)New Faculty Research Fund of Ajou University School of Medicine(to JYC)。
文摘High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and neuroscience.High-mobility group box 1 in the extracellular space functions as a pro-inflammatory damage-associated molecular pattern,which has been proven to play an important role in a wide variety of central nervous system disorders such as ischemic stroke,Alzheimer’s disease,frontotemporal dementia,Parkinson’s disease,multiple sclerosis,epilepsy,and traumatic brain injury.Several drugs that inhibit high-mobility group box 1 as a damage-associated molecular pattern,such as glycyrrhizin,ethyl pyruvate,and neutralizing anti-high-mobility group box 1 antibodies,are commonly used to target high-mobility group box 1 activity in central nervous system disorders.Although it is commonly known for its detrimental inflammatory effect,high-mobility group box 1 has also been shown to have beneficial pro-regenerative roles in central nervous system disorders.In this narrative review,we provide a brief summary of the history of high-mobility group box 1 research and its characterization as a damage-associated molecular pattern,its downstream receptors,and intracellular signaling pathways,how high-mobility group box 1 exerts the repair-favoring roles in general and in the central nervous system,and clues on how to differentiate the pro-regenerative from the pro-inflammatory role.Research targeting high-mobility group box 1 in the central nervous system may benefit from differentiating between the two functions rather than overall suppression of high-mobility group box 1.
文摘背景:既往研究表明,中老年人体内组织蛋白酶K水平可通过影响骨密度来干预骨质疏松的发生和发展,但组织蛋白酶家族与其他人群骨密度之间是否存在因果关系仍未知。目的:探讨组织蛋白酶与骨密度的因果关系。方法:从IEU Open GWAS数据库提取与8种组织蛋白酶相关的遗传位点作为工具变量,以5个年龄段人群的骨密度作为结局。通过双向孟德尔随机化分析,评估组织蛋白酶与骨密度的因果关系。使用Cochran’s Q检验评估遗传工具变量的异质性,使用MR-Egger截距检验评估多效性,使用留一法评估作为工具变量的单核苷酸多态性对暴露和结局因果关系影响的敏感性。结果与结论:①正向孟德尔随机化的逆方差加权法结果显示,组织蛋白酶H与>45岁且≤60岁人群的骨密度呈负相关[OR(95%CI)=0.965(0.94-0.99),P=0.04],组织蛋白酶Z与>30岁且≤45岁人群的骨密度呈负相关[OR(95%CI)=1.06(1.00-1.11),P=0.03];②敏感性分析结果显示因果关系稳定,MR-Egger截距分析未检测到潜在的水平多效性;③反向孟德尔随机化结果显示,骨密度对组织蛋白酶无显著反向作用;④上述结果证实,组织蛋白酶对部分年龄段人群骨密度会造成影响,可能会增加骨质疏松症的发病风险,应给予更多关注。
文摘In his verses, a poet lauded Xiangquan Liquor as "A bibber had a few cups of Xiangquan Liquor, and he became intoxicated for three thousand years. When he sobered up and took his cup again, the bibber became a celestial of wine." The Xiangquan Liquor produced by Hunan Xiangquan Group boasts a unique bouquet distinguishing it in flavour from other name brand spirits on the domestic market. The type of its bouquet, a compound one, is
