Oxidized low-density lipoprotein receptor 1(OLR1)is upregulated in neurons and participates in hypertension-induced neuronal apoptosis.OLR1 deletion exerts protective effects on cerebral damage induced by hypertensive...Oxidized low-density lipoprotein receptor 1(OLR1)is upregulated in neurons and participates in hypertension-induced neuronal apoptosis.OLR1 deletion exerts protective effects on cerebral damage induced by hypertensive-induced stroke.Therefore,OLR1 is likely involved in the progress of intracerebral hemorrhage.In this study,we examined the potential role of OLR1 in intracerebral hemorrhage using a rat model.OLR1 small interfering RNA(10μL;50 pmol/μL)was injected into the right basal ganglia to knock down OLR1.Twenty-four hours later,0.5 U collagenase type VII was injected to induce intracerebral hemorrhage.We found that knockdown of OLR1 attenuated neurological behavior impairment in rats with intracerebral hemorrhage and reduced hematoma,neuron loss,inflammatory reaction,and oxidative stress in rat brain tissue.We also found that silencing of OLR1 suppressed ferroptosis induced by intracerebral hemorrhage and the p38 signaling pathway.Therefore,silencing OLR1 exhibits protective effects against secondary injury of intracerebral hemorrhage.These findings suggest that OLR1 may be a novel potential therapeutic target for intracerebral hemorrhage.展开更多
随着年龄的增长,机体胆固醇代谢失调和叶黄素水平异常易导致视网膜异常脂质沉积和玻璃膜疣,进而增加年龄相关性黄斑变性(age-related macular degeneration,AMD)的患病风险。视网膜细胞上的B类1型清道夫受体(scavenger receptor class B...随着年龄的增长,机体胆固醇代谢失调和叶黄素水平异常易导致视网膜异常脂质沉积和玻璃膜疣,进而增加年龄相关性黄斑变性(age-related macular degeneration,AMD)的患病风险。视网膜细胞上的B类1型清道夫受体(scavenger receptor class B type 1,SR-B1)在脂质代谢和视网膜保护中至关重要。组织细胞表面的SR-B1通过识别并结合细胞外的高密度脂蛋白(high-density lipoprotein,HDL),将游离胆固醇逆向转运至肝脏,对维持全身包括视网膜的脂质代谢平衡与避免脂质沉积至关重要。此外,HDL同样作为转运体参与叶黄素的视网膜转运过程。叶黄素,以其独特的蓝光过滤和抗氧化功能,减少蓝光对视网膜的潜在损伤并清除有害的氧自由基,发挥保护视网膜的作用。本综述将详细探讨SR-B1在视网膜中的作用,尤其是在协助胆固醇清除和叶黄素抗氧化防御方面的重要性,并评述SR-B1以及携带的有益成分如HDL和叶黄素对缓解AMD发病的机制与最新研究进展。展开更多
As the leading cause of worldwide hospital-acquired infection,Clostridioides difficile(C.difficile)infection has caused heavy economic and hospitalized burden,while its pathogenesis is not fully understood.Toxin B(Tcd...As the leading cause of worldwide hospital-acquired infection,Clostridioides difficile(C.difficile)infection has caused heavy economic and hospitalized burden,while its pathogenesis is not fully understood.Toxin B(Tcd B)is one of the major virulent factors of C.difficile.Recently,CSPG4 and FZD2 were reported to be the receptors that mediate Tcd B cellular entry.However,genetic ablation of genes encoding these receptors failed to completely block Tcd B entry,implicating the existence of alternative receptor(s)for this toxin.Here,by employing the CRISPR-Cas9 screen in CSPG4-deficient He La cells,we identified LDL receptor-related protein-1(LRP1)as a novel receptor for Tcd B.Knockout of LRP1 in both CSPG4-deficient He La cells and colonic epithelium Caco2 cells conferred cells with increased Tcd B resistance,while LRP1 overexpression sensitized cells to Tcd B at a low concentration.Co-immunoprecipitation assay showed that LRP1 interacts with full-length Tcd B.Moreover,CROPs domain,which is dispensable for Tcd B’s interaction with CSPG4 and FZD2,is sufficient for binding to LRP1.As such,our study provided evidence for a novel mechanism of Tcd B entry and suggested potential therapeutic targets for treating C.difficile infection.展开更多
目的探讨早发型子痫前期(early onset pre-eclampsia,EOSP)患者血清内皮细胞特异性分子-1(endothelial cell specific molecule-1,ESM1)及低密度脂蛋白受体相关蛋白-1(low-density lipoprotein receptor-related protein-1,LRP1)水平及...目的探讨早发型子痫前期(early onset pre-eclampsia,EOSP)患者血清内皮细胞特异性分子-1(endothelial cell specific molecule-1,ESM1)及低密度脂蛋白受体相关蛋白-1(low-density lipoprotein receptor-related protein-1,LRP1)水平及与病情严重程度的相关性。方法选取2019年2月~2021年2月盐城市妇幼保健院218例早发型子痫前期患者为研究对象(病例组),根据病情分为轻度组(n=117)和重度组(n=101),以同期健康体检的80例健康孕妇为对照组。比较各组血清ESM1和LRP1水平。采用多因素Logistic回归分析早发型子痫前期病情严重程度的影响因素。绘制受试者工作曲线分析血清ESM1和LRP1对早发型重度子痫前期的诊断价值。结果病例组血清ESM1(323.05±45.17 mmol/L),LRP1(12.25±0.97μg/ml)水平高于对照组(195.20±31.67 mmol/L,6.41±0.84μg/ml),差异具有统计学意义(t=23.291,47.677,均P<0.05)。重度组患者血清ESM1(672.44±83.61 pg/ml),血清LRP1(14.52±1.05μg/ml)、舒张压(113.17±12.24mmHg)、收缩压(165.19±16.63mmHg)、24h尿蛋白量(2.63±0.45g/24h)、血肌酐(74.47±20.82μmol/L)、血尿素氮(4.32±0.78mmol/L)、血尿酸(339.65±50.13μmol/L)高于轻度组(551.74±72.20 pg/ml,9.63±0.89μg/ml,92.41±9.29mmHg,147.25±14.66mmHg,1.42±0.33g/24h,69.64±15.07μmol/L,3.95±0.91mmol/L,303.82±41.71μmol/L),新生儿体质量低于轻度组(2.73±0.62 kg vs 3.20±0.62 kg),差异具有统计学意义(t=1.980~37.978,均P<0.05)。病例组患者血清ESM1及LRP1水平与舒张压、收缩压、24h尿蛋白定量、血肌酐、血尿素氮及血尿酸呈正相关(r=0.413~0.515,均P<0.05),与胎儿体质量呈负相关(r=-0.563,-0.604,均P<0.05)。高血清ESM1水平(OR=1.217,95%CI:1.036~1.429)和高血清LRP1水平(OR=1.486,95%CI:1.056~2.090)是影响早发型重度子痫前期发生的独立危险因素。血清ESM1联合LRP1诊断早发型重度子痫前期的曲线下面积(area under the curve,AUC)0.884(0.853~0.916)大于ESM1(AUC=0.749,95%CI:0.705~0.792)和LRP1(AUC=0.760,95%CI:0.712~0.807)单独诊断(Z=6.752,4.297,均P<0.05)。结论早发型子痫前期患者血清ESM1和LRP1水平升高,二者均与早发型子痫前期疾病严重程度有关,联合检测能提高早发型重度子痫前期的诊断效能。展开更多
低密度脂蛋白受体相关蛋白1(low density lipoprotein receptor related protein 1,LRP1),也被称为CD91或α2巨球蛋白受体,是一种普遍表达于细胞表面的大分子量内吞性受体,属于低密度脂蛋白受体家族的成员之一。LRP1主要参与细胞的两个...低密度脂蛋白受体相关蛋白1(low density lipoprotein receptor related protein 1,LRP1),也被称为CD91或α2巨球蛋白受体,是一种普遍表达于细胞表面的大分子量内吞性受体,属于低密度脂蛋白受体家族的成员之一。LRP1主要参与细胞的两个生理过程:内吞作用和信号通路的调控。许多结构和功能不同的蛋白质都可以作为其配体而被内吞至细胞内;LRP1还可作为信号受体与胞质内蛋白质结合而调控信号通路。因此,LRP1在细胞的病理生理过程中发挥重要作用。在心血管疾病中,LRP1可通过其独特的功能参与疾病的发生发展,并可能成为心血管疾病治疗的新靶点。展开更多
目的研究脑微出血(cerebral microbleeds,CMBs)患者1,25-二羟维生素D3[1,25-dihydroxyvitamin D3,1,25-(OH)2D3],可溶性低密度脂蛋白受体相关蛋白1(soluble low density lipoprotein receptor related protein 1,sLRP1)水平与头颅SWI微...目的研究脑微出血(cerebral microbleeds,CMBs)患者1,25-二羟维生素D3[1,25-dihydroxyvitamin D3,1,25-(OH)2D3],可溶性低密度脂蛋白受体相关蛋白1(soluble low density lipoprotein receptor related protein 1,sLRP1)水平与头颅SWI微出血病灶数量及部位等影像学特征的相关关系。方法连续纳入2017年1月~2019年5月就诊于陕西省人民医院的CMBs患者196例(男性152例,女性44例),正常对照组99例(男性67例,女性32例),采集人口学资料及病史。对两组人群进行血浆1,25-(OH)2D3,sLRP1水平的检查。比较两组间血浆1,25-(OH)2D3和sLRP1水平的差异,并统计CMBs组各检验指标与CMBs病灶数量及部位的相关关系。结果CMBs组患者血浆1,25-(OH)2D3,sLRP1水平均低于对照组(23.32±18.91 mmol/L vs 39.60±18.58 mmol/L;237.96±70.62 ng/ml vs 312.61±62.78 ng/ml),差异均具有统计学意义(t=7.07,-9.24,均P<0.01)。CMBs患者血浆sLRP1水平与脑皮质CMBs病灶数量呈负相关(r=0.239,P=0.001),而与脑深部CMBs病灶数量无明显相关(t=-0.096,P>0.05)。结论CMBs患者的血浆1,25-(OH)2D3,sLRP1水平均低于正常人群。高表达的血浆sLRP1可能对脑皮质CMBs的发生具有一定的保护作用。展开更多
基金supported by the National Natural Science Foundation of China,No.81971125(to ZYH).
文摘Oxidized low-density lipoprotein receptor 1(OLR1)is upregulated in neurons and participates in hypertension-induced neuronal apoptosis.OLR1 deletion exerts protective effects on cerebral damage induced by hypertensive-induced stroke.Therefore,OLR1 is likely involved in the progress of intracerebral hemorrhage.In this study,we examined the potential role of OLR1 in intracerebral hemorrhage using a rat model.OLR1 small interfering RNA(10μL;50 pmol/μL)was injected into the right basal ganglia to knock down OLR1.Twenty-four hours later,0.5 U collagenase type VII was injected to induce intracerebral hemorrhage.We found that knockdown of OLR1 attenuated neurological behavior impairment in rats with intracerebral hemorrhage and reduced hematoma,neuron loss,inflammatory reaction,and oxidative stress in rat brain tissue.We also found that silencing of OLR1 suppressed ferroptosis induced by intracerebral hemorrhage and the p38 signaling pathway.Therefore,silencing OLR1 exhibits protective effects against secondary injury of intracerebral hemorrhage.These findings suggest that OLR1 may be a novel potential therapeutic target for intracerebral hemorrhage.
文摘随着年龄的增长,机体胆固醇代谢失调和叶黄素水平异常易导致视网膜异常脂质沉积和玻璃膜疣,进而增加年龄相关性黄斑变性(age-related macular degeneration,AMD)的患病风险。视网膜细胞上的B类1型清道夫受体(scavenger receptor class B type 1,SR-B1)在脂质代谢和视网膜保护中至关重要。组织细胞表面的SR-B1通过识别并结合细胞外的高密度脂蛋白(high-density lipoprotein,HDL),将游离胆固醇逆向转运至肝脏,对维持全身包括视网膜的脂质代谢平衡与避免脂质沉积至关重要。此外,HDL同样作为转运体参与叶黄素的视网膜转运过程。叶黄素,以其独特的蓝光过滤和抗氧化功能,减少蓝光对视网膜的潜在损伤并清除有害的氧自由基,发挥保护视网膜的作用。本综述将详细探讨SR-B1在视网膜中的作用,尤其是在协助胆固醇清除和叶黄素抗氧化防御方面的重要性,并评述SR-B1以及携带的有益成分如HDL和叶黄素对缓解AMD发病的机制与最新研究进展。
基金supported by the National Natural Science Foundation of China(NSFC31430025)the Beijing Advanced Innovation Center for Genomics at Peking Universitythe Peking-Tsinghua Center for Life Sciences。
文摘As the leading cause of worldwide hospital-acquired infection,Clostridioides difficile(C.difficile)infection has caused heavy economic and hospitalized burden,while its pathogenesis is not fully understood.Toxin B(Tcd B)is one of the major virulent factors of C.difficile.Recently,CSPG4 and FZD2 were reported to be the receptors that mediate Tcd B cellular entry.However,genetic ablation of genes encoding these receptors failed to completely block Tcd B entry,implicating the existence of alternative receptor(s)for this toxin.Here,by employing the CRISPR-Cas9 screen in CSPG4-deficient He La cells,we identified LDL receptor-related protein-1(LRP1)as a novel receptor for Tcd B.Knockout of LRP1 in both CSPG4-deficient He La cells and colonic epithelium Caco2 cells conferred cells with increased Tcd B resistance,while LRP1 overexpression sensitized cells to Tcd B at a low concentration.Co-immunoprecipitation assay showed that LRP1 interacts with full-length Tcd B.Moreover,CROPs domain,which is dispensable for Tcd B’s interaction with CSPG4 and FZD2,is sufficient for binding to LRP1.As such,our study provided evidence for a novel mechanism of Tcd B entry and suggested potential therapeutic targets for treating C.difficile infection.
文摘目的探讨早发型子痫前期(early onset pre-eclampsia,EOSP)患者血清内皮细胞特异性分子-1(endothelial cell specific molecule-1,ESM1)及低密度脂蛋白受体相关蛋白-1(low-density lipoprotein receptor-related protein-1,LRP1)水平及与病情严重程度的相关性。方法选取2019年2月~2021年2月盐城市妇幼保健院218例早发型子痫前期患者为研究对象(病例组),根据病情分为轻度组(n=117)和重度组(n=101),以同期健康体检的80例健康孕妇为对照组。比较各组血清ESM1和LRP1水平。采用多因素Logistic回归分析早发型子痫前期病情严重程度的影响因素。绘制受试者工作曲线分析血清ESM1和LRP1对早发型重度子痫前期的诊断价值。结果病例组血清ESM1(323.05±45.17 mmol/L),LRP1(12.25±0.97μg/ml)水平高于对照组(195.20±31.67 mmol/L,6.41±0.84μg/ml),差异具有统计学意义(t=23.291,47.677,均P<0.05)。重度组患者血清ESM1(672.44±83.61 pg/ml),血清LRP1(14.52±1.05μg/ml)、舒张压(113.17±12.24mmHg)、收缩压(165.19±16.63mmHg)、24h尿蛋白量(2.63±0.45g/24h)、血肌酐(74.47±20.82μmol/L)、血尿素氮(4.32±0.78mmol/L)、血尿酸(339.65±50.13μmol/L)高于轻度组(551.74±72.20 pg/ml,9.63±0.89μg/ml,92.41±9.29mmHg,147.25±14.66mmHg,1.42±0.33g/24h,69.64±15.07μmol/L,3.95±0.91mmol/L,303.82±41.71μmol/L),新生儿体质量低于轻度组(2.73±0.62 kg vs 3.20±0.62 kg),差异具有统计学意义(t=1.980~37.978,均P<0.05)。病例组患者血清ESM1及LRP1水平与舒张压、收缩压、24h尿蛋白定量、血肌酐、血尿素氮及血尿酸呈正相关(r=0.413~0.515,均P<0.05),与胎儿体质量呈负相关(r=-0.563,-0.604,均P<0.05)。高血清ESM1水平(OR=1.217,95%CI:1.036~1.429)和高血清LRP1水平(OR=1.486,95%CI:1.056~2.090)是影响早发型重度子痫前期发生的独立危险因素。血清ESM1联合LRP1诊断早发型重度子痫前期的曲线下面积(area under the curve,AUC)0.884(0.853~0.916)大于ESM1(AUC=0.749,95%CI:0.705~0.792)和LRP1(AUC=0.760,95%CI:0.712~0.807)单独诊断(Z=6.752,4.297,均P<0.05)。结论早发型子痫前期患者血清ESM1和LRP1水平升高,二者均与早发型子痫前期疾病严重程度有关,联合检测能提高早发型重度子痫前期的诊断效能。
文摘低密度脂蛋白受体相关蛋白1(low density lipoprotein receptor related protein 1,LRP1),也被称为CD91或α2巨球蛋白受体,是一种普遍表达于细胞表面的大分子量内吞性受体,属于低密度脂蛋白受体家族的成员之一。LRP1主要参与细胞的两个生理过程:内吞作用和信号通路的调控。许多结构和功能不同的蛋白质都可以作为其配体而被内吞至细胞内;LRP1还可作为信号受体与胞质内蛋白质结合而调控信号通路。因此,LRP1在细胞的病理生理过程中发挥重要作用。在心血管疾病中,LRP1可通过其独特的功能参与疾病的发生发展,并可能成为心血管疾病治疗的新靶点。
文摘目的研究脑微出血(cerebral microbleeds,CMBs)患者1,25-二羟维生素D3[1,25-dihydroxyvitamin D3,1,25-(OH)2D3],可溶性低密度脂蛋白受体相关蛋白1(soluble low density lipoprotein receptor related protein 1,sLRP1)水平与头颅SWI微出血病灶数量及部位等影像学特征的相关关系。方法连续纳入2017年1月~2019年5月就诊于陕西省人民医院的CMBs患者196例(男性152例,女性44例),正常对照组99例(男性67例,女性32例),采集人口学资料及病史。对两组人群进行血浆1,25-(OH)2D3,sLRP1水平的检查。比较两组间血浆1,25-(OH)2D3和sLRP1水平的差异,并统计CMBs组各检验指标与CMBs病灶数量及部位的相关关系。结果CMBs组患者血浆1,25-(OH)2D3,sLRP1水平均低于对照组(23.32±18.91 mmol/L vs 39.60±18.58 mmol/L;237.96±70.62 ng/ml vs 312.61±62.78 ng/ml),差异均具有统计学意义(t=7.07,-9.24,均P<0.01)。CMBs患者血浆sLRP1水平与脑皮质CMBs病灶数量呈负相关(r=0.239,P=0.001),而与脑深部CMBs病灶数量无明显相关(t=-0.096,P>0.05)。结论CMBs患者的血浆1,25-(OH)2D3,sLRP1水平均低于正常人群。高表达的血浆sLRP1可能对脑皮质CMBs的发生具有一定的保护作用。
