Sorafenib,a multikinase inhibitor used for the treatment of hepatocellular carcinoma,is limited by its low oral bioavailability.To overcome this drawback,we have developed novel camel milk casein-derived nanoparticles...Sorafenib,a multikinase inhibitor used for the treatment of hepatocellular carcinoma,is limited by its low oral bioavailability.To overcome this drawback,we have developed novel camel milk casein-derived nanoparticles as a drug delivery system.Camel milk casein is not only biocompatible on oral administration but is actually a dietary protein of pharmaceutical relevance.Casein is used because of its amphiphilic nature,self-assembling property,ability to show sustained release,and capability of encapsulating both hydrophilic and hydrophobic drugs.In this study,camel milk casein nanoparticles loaded with sorafenib were developed and characterized.Characterization of casein nanoparticles was done by dynamic light scattering(DLS),zeta potential analysis,scanning light microscopy(SEM),and FTIR.The drug content in nanoparticle and drug-protein binding studies were conducted by UV spectroscopy.The cytotoxicity and cellular uptake efficiency studies were performed in HepG2 cell lines.It was observed that the cytotoxic effect of sorafenib loaded camel milk casein nanoparticles was more than free sorafenib in HepG2 cells.This work suggests camel milk casein as a suitable drug delivery molecule for sorafenib.In the future,it may also be used in enhancing the efficacy and specific distribution of other water-insoluble anticancer drugs.展开更多
Protein phosphorylation is an important post-translational modification that regulates milk protein structure and function.The objective of this study was to analyze the presence of phosphorylated casein.Bovine milk p...Protein phosphorylation is an important post-translational modification that regulates milk protein structure and function.The objective of this study was to analyze the presence of phosphorylated casein.Bovine milk proteins were first separated by SDS polyacrylamide gel electrophoresis.After in gels digestion and extraction,phosphorylated peptides were enriched by titanium dioxide and identified by ultra performance liquid chromatography coupled with nano electrospray ionization tandem mass spectrometry.This method ensured the identification of 20 phosphorylated peptides,including 7 phosphorylated forms of α_s1-casein,8 α_s2-casein,and 5 β-casein.Eight phosphorylated sites derived from 3 α_s1-caseins,3 α_s2-caseins,and 2 β-caseins were also identified,and localized on residues Ser^61,Ser^63 and Ser^130 in α_s1-casein;Thr^145,Ser^146 and Ser^158 in α_s2-casein;and Ser^50 and Thr^56 in β-casein.These findings provide valuable information for investigating casein phosphorylation of the bovine milk.展开更多
常温再制干酪制品是指经超高温瞬时灭菌(Ultra-high temperature treated, UHT)处理后可常温贮藏的灭菌型干酪制品,是我国乳品工业的新热点。然而,干酪在UHT处理后易失稳发生凝胶结构重构,在贮藏期间出现析水等质构问题,影响产品品质。...常温再制干酪制品是指经超高温瞬时灭菌(Ultra-high temperature treated, UHT)处理后可常温贮藏的灭菌型干酪制品,是我国乳品工业的新热点。然而,干酪在UHT处理后易失稳发生凝胶结构重构,在贮藏期间出现析水等质构问题,影响产品品质。为阐明蛋白原料对常温再制干酪制品析水性的影响及机制,筛选了3种不同的蛋白原料:膜过滤酪蛋白胶束、浓缩牛奶蛋白、凝乳酶酪蛋白,分析其蛋白质含量、组成以及粒径、电位、水合性和钙离子分布等理化特性,进而分析了蛋白原料对常温再制干酪制品析水性和质构特性的影响规律,并从水分分布和微观结构层面解析蛋白原料对常温再制干酪制品析水性的影响机制。结果表明:3种蛋白原料的蛋白质含量和组成存在显著差异,浓缩牛奶蛋白的乳清蛋白占总蛋白质量分数比膜过滤酪蛋白胶束高7.81个百分点,而凝乳酶酪蛋白中不含乳清蛋白;在水合性方面,浓缩牛奶蛋白和膜过滤酪蛋白胶束相近,均显著高于凝乳酶酪蛋白。蛋白原料显著影响常温再制干酪制品析水性,贮藏90 d时,由凝乳酶酪蛋白制备的常温再制干酪制品析水率最高,而由浓缩牛奶蛋白制备的常温再制干酪制品的析水率最低,表面析水率和离心析水率分别为0.42%和1.10%。水分分布和微观结构结果显示,蛋白原料通过影响干酪制品中水分的存在状态和三维网络空间结构,从而影响常温再制干酪制品的析水性。研究解析了不同蛋白原料对常温再制干酪制品析水性的影响及机制,为常温再制干酪制品析水性的改善提供了理论依据。展开更多
文摘Sorafenib,a multikinase inhibitor used for the treatment of hepatocellular carcinoma,is limited by its low oral bioavailability.To overcome this drawback,we have developed novel camel milk casein-derived nanoparticles as a drug delivery system.Camel milk casein is not only biocompatible on oral administration but is actually a dietary protein of pharmaceutical relevance.Casein is used because of its amphiphilic nature,self-assembling property,ability to show sustained release,and capability of encapsulating both hydrophilic and hydrophobic drugs.In this study,camel milk casein nanoparticles loaded with sorafenib were developed and characterized.Characterization of casein nanoparticles was done by dynamic light scattering(DLS),zeta potential analysis,scanning light microscopy(SEM),and FTIR.The drug content in nanoparticle and drug-protein binding studies were conducted by UV spectroscopy.The cytotoxicity and cellular uptake efficiency studies were performed in HepG2 cell lines.It was observed that the cytotoxic effect of sorafenib loaded camel milk casein nanoparticles was more than free sorafenib in HepG2 cells.This work suggests camel milk casein as a suitable drug delivery molecule for sorafenib.In the future,it may also be used in enhancing the efficacy and specific distribution of other water-insoluble anticancer drugs.
基金supported by an earmark fund for the National Key Basic Research Program of China(2011CB100805)
文摘Protein phosphorylation is an important post-translational modification that regulates milk protein structure and function.The objective of this study was to analyze the presence of phosphorylated casein.Bovine milk proteins were first separated by SDS polyacrylamide gel electrophoresis.After in gels digestion and extraction,phosphorylated peptides were enriched by titanium dioxide and identified by ultra performance liquid chromatography coupled with nano electrospray ionization tandem mass spectrometry.This method ensured the identification of 20 phosphorylated peptides,including 7 phosphorylated forms of α_s1-casein,8 α_s2-casein,and 5 β-casein.Eight phosphorylated sites derived from 3 α_s1-caseins,3 α_s2-caseins,and 2 β-caseins were also identified,and localized on residues Ser^61,Ser^63 and Ser^130 in α_s1-casein;Thr^145,Ser^146 and Ser^158 in α_s2-casein;and Ser^50 and Thr^56 in β-casein.These findings provide valuable information for investigating casein phosphorylation of the bovine milk.
文摘常温再制干酪制品是指经超高温瞬时灭菌(Ultra-high temperature treated, UHT)处理后可常温贮藏的灭菌型干酪制品,是我国乳品工业的新热点。然而,干酪在UHT处理后易失稳发生凝胶结构重构,在贮藏期间出现析水等质构问题,影响产品品质。为阐明蛋白原料对常温再制干酪制品析水性的影响及机制,筛选了3种不同的蛋白原料:膜过滤酪蛋白胶束、浓缩牛奶蛋白、凝乳酶酪蛋白,分析其蛋白质含量、组成以及粒径、电位、水合性和钙离子分布等理化特性,进而分析了蛋白原料对常温再制干酪制品析水性和质构特性的影响规律,并从水分分布和微观结构层面解析蛋白原料对常温再制干酪制品析水性的影响机制。结果表明:3种蛋白原料的蛋白质含量和组成存在显著差异,浓缩牛奶蛋白的乳清蛋白占总蛋白质量分数比膜过滤酪蛋白胶束高7.81个百分点,而凝乳酶酪蛋白中不含乳清蛋白;在水合性方面,浓缩牛奶蛋白和膜过滤酪蛋白胶束相近,均显著高于凝乳酶酪蛋白。蛋白原料显著影响常温再制干酪制品析水性,贮藏90 d时,由凝乳酶酪蛋白制备的常温再制干酪制品析水率最高,而由浓缩牛奶蛋白制备的常温再制干酪制品的析水率最低,表面析水率和离心析水率分别为0.42%和1.10%。水分分布和微观结构结果显示,蛋白原料通过影响干酪制品中水分的存在状态和三维网络空间结构,从而影响常温再制干酪制品的析水性。研究解析了不同蛋白原料对常温再制干酪制品析水性的影响及机制,为常温再制干酪制品析水性的改善提供了理论依据。
