赖氨酰氧化酶样蛋白4(lysyl oxidase like 4,LOXL4)是一种属于赖氨酰氧化酶(lysyl oxidase,LOX)蛋白质家族的分泌型铜依赖性胺氧化酶,参与细胞外基质(extracellular matrix,ECM)的组装和维持。LOXL4蛋白在人类肝癌、胃癌、乳腺癌、宫颈...赖氨酰氧化酶样蛋白4(lysyl oxidase like 4,LOXL4)是一种属于赖氨酰氧化酶(lysyl oxidase,LOX)蛋白质家族的分泌型铜依赖性胺氧化酶,参与细胞外基质(extracellular matrix,ECM)的组装和维持。LOXL4蛋白在人类肝癌、胃癌、乳腺癌、宫颈癌、头颈鳞癌、食管癌和结直肠癌中表达上调,而在人类膀胱癌和肺癌中表达下调并抑制肿瘤的生长,表明LOXL4蛋白在不同类型的人类恶性肿瘤中具有促癌或抑癌的双向作用。肿瘤细胞外泌体中的LOXL4蛋白通过催化作用产生过氧化氢,后者直接激活FAK/Src信号通路,并促进细胞基质粘附和细胞迁移。外泌体介导的LOXL4还可以通过激活PI3K/Akt信号通路来促进肿瘤细胞的增殖和免疫逃逸。肿瘤细胞中的LOXL4可以经外泌体转运至巨噬细胞,进一步通过STAT1和STAT3介导的信号通路激活细胞免疫抑制功能和激活程序性死亡配体1(programmed death ligand 1,PD-L1)表达,触发巨噬细胞的免疫抑制功能,促进肿瘤细胞的免疫逃逸。此外,LOXL4蛋白还能通过激活p53蛋白和抑制Ras/ERK信号转导通路发挥抑癌功能。本文主要总结了LOXL4蛋白的结构、功能及其在人类恶性肿瘤发生发展的作用机制,进一步探讨LOXL4蛋白在恶性肿瘤研究中的应用前景,为恶性肿瘤的临床诊断、治疗和筛选预后标志物提供理论基础和参考依据。展开更多
Silica biomaterials including Bioglass offer great biocompatibility and bioactivity but fail to provide pore and degradation features needed for tissue engineering.Herein we report on the synthesis and characterizatio...Silica biomaterials including Bioglass offer great biocompatibility and bioactivity but fail to provide pore and degradation features needed for tissue engineering.Herein we report on the synthesis and characterization of novel amorphous silica fiber matrices to overcome these limitations.Amorphous silica fibers were fused by sintering to produce porous matrices.The effects of sacrificial polymer additives such as polyvinyl alcohol(PVA)and cellulose fibers(CF)on the sintering process were also studied.The resulting matrices formed between sintering temperatures of 1,350-1,550◦C retained their fiber structures.The matrices presented pores in the range of 50-200μm while higher sintering temperatures resulted in increased pore diameter.PVA addition to silica significantly reduced the pore diameter and porosity compared with silica matrices with or without the addition of CF.The PVA additive morphologically appeared to fuse the silica fibers to a greater extent and resulted in significantly higher compressive modulus and strength than the rest of the matrices synthesized.These matrices lost roughly 30%of their original mass in an in vitro degradation study over 40 weeks.All matrices absorbed 500 wt%of water and did not change in their overall morphology,size,or shape with hydration.These fiber matrices supported human mesenchymal stem cell adhesion,proliferation,and mineralized matrix production.Amorphous silica fiber biomaterials/matrices reported here are biodegradable and porous and closely resemble the native extracellular matrix structure and water absorption capacity.Extending the methodology reported here to alter matrix properties may lead to a variety of tissue engineering,implant,and drug delivery applications.展开更多
文摘赖氨酰氧化酶样蛋白4(lysyl oxidase like 4,LOXL4)是一种属于赖氨酰氧化酶(lysyl oxidase,LOX)蛋白质家族的分泌型铜依赖性胺氧化酶,参与细胞外基质(extracellular matrix,ECM)的组装和维持。LOXL4蛋白在人类肝癌、胃癌、乳腺癌、宫颈癌、头颈鳞癌、食管癌和结直肠癌中表达上调,而在人类膀胱癌和肺癌中表达下调并抑制肿瘤的生长,表明LOXL4蛋白在不同类型的人类恶性肿瘤中具有促癌或抑癌的双向作用。肿瘤细胞外泌体中的LOXL4蛋白通过催化作用产生过氧化氢,后者直接激活FAK/Src信号通路,并促进细胞基质粘附和细胞迁移。外泌体介导的LOXL4还可以通过激活PI3K/Akt信号通路来促进肿瘤细胞的增殖和免疫逃逸。肿瘤细胞中的LOXL4可以经外泌体转运至巨噬细胞,进一步通过STAT1和STAT3介导的信号通路激活细胞免疫抑制功能和激活程序性死亡配体1(programmed death ligand 1,PD-L1)表达,触发巨噬细胞的免疫抑制功能,促进肿瘤细胞的免疫逃逸。此外,LOXL4蛋白还能通过激活p53蛋白和抑制Ras/ERK信号转导通路发挥抑癌功能。本文主要总结了LOXL4蛋白的结构、功能及其在人类恶性肿瘤发生发展的作用机制,进一步探讨LOXL4蛋白在恶性肿瘤研究中的应用前景,为恶性肿瘤的临床诊断、治疗和筛选预后标志物提供理论基础和参考依据。
基金support from the National Institute of Biomedical Imaging and Bioengineering(NIBIB)of the National Institutes of Health(#R01EB030060&#R01EB020640)Dr.Nukavarapu also acknowledges funding from NSF EFMA(#1908454).
文摘Silica biomaterials including Bioglass offer great biocompatibility and bioactivity but fail to provide pore and degradation features needed for tissue engineering.Herein we report on the synthesis and characterization of novel amorphous silica fiber matrices to overcome these limitations.Amorphous silica fibers were fused by sintering to produce porous matrices.The effects of sacrificial polymer additives such as polyvinyl alcohol(PVA)and cellulose fibers(CF)on the sintering process were also studied.The resulting matrices formed between sintering temperatures of 1,350-1,550◦C retained their fiber structures.The matrices presented pores in the range of 50-200μm while higher sintering temperatures resulted in increased pore diameter.PVA addition to silica significantly reduced the pore diameter and porosity compared with silica matrices with or without the addition of CF.The PVA additive morphologically appeared to fuse the silica fibers to a greater extent and resulted in significantly higher compressive modulus and strength than the rest of the matrices synthesized.These matrices lost roughly 30%of their original mass in an in vitro degradation study over 40 weeks.All matrices absorbed 500 wt%of water and did not change in their overall morphology,size,or shape with hydration.These fiber matrices supported human mesenchymal stem cell adhesion,proliferation,and mineralized matrix production.Amorphous silica fiber biomaterials/matrices reported here are biodegradable and porous and closely resemble the native extracellular matrix structure and water absorption capacity.Extending the methodology reported here to alter matrix properties may lead to a variety of tissue engineering,implant,and drug delivery applications.
