Nonalcoholic fatty liver disease,recently termed metabolic dysfunction-associated steatotic liver disease,affects 25%of adults globally,with a prevalence reaching 93%in obese individuals.The MANPOWER study,a post hoc ...Nonalcoholic fatty liver disease,recently termed metabolic dysfunction-associated steatotic liver disease,affects 25%of adults globally,with a prevalence reaching 93%in obese individuals.The MANPOWER study,a post hoc analysis of 2843 Russian patients with newly diagnosed nonalcoholic fatty liver disease,evaluated Essentiale Forte N®[essential phospholipids(EPLs)]therapy and a liver enzymebased staging algorithm.Using generalized linear regression and McNemar tests,EPLs reduced liver enzyme levels(alanine aminotransferase:-20.4 U/L,aspartate aminotransferase:-16.9 U/L,gamma-glutamyl transferase:-17.1 U/L at 24 weeks,P<0.001)and improved ultrasonography findings(76.8%reduction in hyperechogenicity,P<0.001).A logistic regression algorithm using alanine aminotransferase,aspartate aminotransferase,and gamma-glutamyl transferase levels achieved 72.3%accuracy,75.6%sensitivity,71.0%specificity,and an area under the receiver operating characteristic curve of 0.74(95%confidence interval:0.71-0.77)for identifying nonalcoholic steatohepatitis.These findings advocate EPLs as a safe,effective therapy and propose a scalable diagnostic tool,urging validation to reduce the reliance on biopsy.展开更多
BACKGROUND Since non-alcoholic fatty liver disease(NAFLD)is associated with abnormal liver function tests,treatment recommendations aim to reduce the level of known markers of liver inflammation,such as alanine transa...BACKGROUND Since non-alcoholic fatty liver disease(NAFLD)is associated with abnormal liver function tests,treatment recommendations aim to reduce the level of known markers of liver inflammation,such as alanine transaminase(ALT),aspartate transaminase(AST)and gamma-glutamyl transferase(GGT).Essential phospholipids(EPLs)have been shown to reduce levels of these liver enzymes and improve ultrasonographic features.While non-invasive diagnostic tests have been developed to stage inflammation,these tests were not specifically designed to evaluate patients with NAFLD.This highlights the need to describe the liver enzyme profile across the different levels of NAFLD severity for improved grading and staging of NAFLD.AIM To describe liver enzyme profiles across NAFLD severity to inform a diagnostic staging algorithm and identify who may benefit from EPLs.METHODS This post-hoc analysis of the observational MANPOWER study included 2843 adult patients with newly diagnosed NAFLD.The primary endpoint was assessment of baseline liver enzyme profiles.Secondary endpoints were effectiveness of Essentiale®(an EPL)on liver enzyme levels and ultrasonography findings across three definitions of NAFLD:(1)Statistical distribution of liver enzyme levels;(2)MANPOWER cut-offs;and(3)Presence of physiciandiagnosed non-alcoholic steatohepatitis.The best performing algorithm was used to describe the risk factors and profiles associated with increased liver enzyme levels.RESULTS Of the 2843 patients included in this post-hoc analysis,most were female(62.2%),with a mean age of 48.4 years(SD 8.59 years).Overall,mean levels of ALT,AST and GGT increased with NAFLD severity for all three subgroups,with the rate of chronic comorbidities correlated with NAFLD severity.Across each subgroup of interest,Essentiale significantly reduced average liver enzyme levels and improved ultrasonography features,including diffuse liver hyperechogenicity and heterogeneous liver structure(P<0.05),with greater benefit associated with increased severity.Compared with all algorithms tested,the algorithm based on the statistical distribution of liver enzymes displayed the highest accuracy,sensitivity and specificity for the grading and staging of NAFLD and could form the basis of a diagnostic algorithm.CONCLUSION Liver enzyme profiles may identify NAFLD severity and allow monitoring of therapeutic response.Essentiale may improve liver enzyme levels and ultrasonography features.An algorithm could aid in the diagnosis/staging of NAFLD.展开更多
Liposomes were prepared with natural soybean phospholipids by extrusion method after rotating-film evaporating technique. Transmission electron micrography was used to detect the appearances of the prepared liposomes,...Liposomes were prepared with natural soybean phospholipids by extrusion method after rotating-film evaporating technique. Transmission electron micrography was used to detect the appearances of the prepared liposomes, and the liposome diameter was also measured. The prepared liposomes were sphere in shape with the mean diameter of 217 nm and span of 0.838. The phospholipid bilayer structure, suitable for entrapping various effector molecules, could be seen clearly under transmission electron microscopy. The bile salts of sodium cholate and sodium deoxycholate were used as the surfactants to investigate their interaction with liposomes. The turbidities for the mixture of bile salts and liposomes were evaluated by the visible spectrometry method at the wavelength of 500 nm. And the diameter changes of liposomes were also tested to examine the effect of bile salts on liposomes. At the beginning, the diameters and turbidities of liposomes increased a little as the result of mixed micelles formation during the different stages for the structure changes of surfactant-liposomes micelles. The further added bile salts decreased the diameters and turbidities of liposomes. The liposome suspension underwent several rearrangements before small mixed micelles formed. And the diameter of liposomes changed regularly. The interaction of bile salts and liposomes is important for the further study of the behaviors of liposomes in vivo. The drug loaded and release properties of liposomes can also be well reflected by the interaction of liposomes and surfactants.展开更多
[Objective] The research aimed to determine the existence of free phospholipids in the plasma of three species of freshwater fish and lay the foundation for discussing the physiological mechanism of coagulation phenom...[Objective] The research aimed to determine the existence of free phospholipids in the plasma of three species of freshwater fish and lay the foundation for discussing the physiological mechanism of coagulation phenomena in three species of freshwater fish.[Method] The activity of heated phospholipids was detected by the availability test of heated rabbit cephalin.Small amount of the platelet-poor plasma of the rabbit Oryctolagus cuniculus,the cell-free plasma of the carp Cyprinus carpio,the crucian Carassi...展开更多
本研究开发了以乳清分离蛋白(whey protein isolate,WPI)和二十二碳六烯酸磷脂(docosahexaenoic acid-containing phospholipid,DHAPL)为复合乳化剂的水包油(oil-in-water,O/W)乳液,用于包封岩藻黄质(fucoxanthin,FX),旨在提升其热稳定...本研究开发了以乳清分离蛋白(whey protein isolate,WPI)和二十二碳六烯酸磷脂(docosahexaenoic acid-containing phospholipid,DHAPL)为复合乳化剂的水包油(oil-in-water,O/W)乳液,用于包封岩藻黄质(fucoxanthin,FX),旨在提升其热稳定性、抗氧化能力、生物可及性以及对RAW264.7巨噬细胞氧化损伤的保护作用。DHAPL-WPI复合物表现出优异的包封率(>94%),远超传统的单一WPI体系,其中长链DHAPL(如DHAPL-MP/MG)效果较优。该杂化乳化剂结构赋予乳液卓越的热稳定性,在严苛条件(75℃/0.5 h)下仍能保持超过80%的FX完整性,并在25℃条件下展现出优异的贮藏稳定性。此外,DHAPL-WPI体系克服了疏水性生物活性物质生物利用度的关键限制,在体外模拟消化中实现了70%的FX生物可及性,较游离FX提高了1.8倍。复合物的双界面抗氧化机制显著增强了自由基清除能力,使2,2’-联氮双(3-乙基苯并噻唑啉-6-磺酸)阳离子自由基清除率、1,1-二苯基-2-三硝基苯肼自由基清除率提高了35%~42%,同时为RAW264.7巨噬细胞提供了强大的抗氧化应激保护作用,其中,中短链DHAPL效果更优异。本研究构建的生物活性物质负载体系为功能性食品开发提供了一种有效的包封解决方案,成功克服了食品的疏水性活性成分在热加工过程中不稳定和肠道吸收效率低的双重瓶颈问题。展开更多
Phosphatidylethanolamine is a major phospholipid class abundant in the brain,particularly in the inner leaflet of the plasma and mitochondrial membranes.Although it is primarily synthesized from phosphatidylserine via...Phosphatidylethanolamine is a major phospholipid class abundant in the brain,particularly in the inner leaflet of the plasma and mitochondrial membranes.Although it is primarily synthesized from phosphatidylserine via decarboxylation in mitochondria or from ethanolamine via the cytidine diphosphate-ethanolamine pathway in the endoplasmic reticulum,phosphatidylethanolamine that resides in mitochondria is preferentially produced locally and is distinct and separate from the pool of phosphatidylethanolamine made in the endoplasmic reticulum.Mitochondria-derived phosphatidylethanolamine is not only essential for mitochondrial integrity but also is exported to other organelles to fulfill diverse cellular functions.Neurons are highly enriched with phosphatidylethanolamine,and the importance of phosphatidylethanolamine metabolism in neuronal health has recently been recognized following its reported links to Alzheimer’s disease,Parkinson’s disease,and hereditary spastic paraplegia,among other neurological disorders.Indeed,disturbances in mitochondrial function and phosphatidylethanolamine metabolism and the resulting neuronal dysfunction are the common features of individuals suffering from these diseases,highlighting the great importance of maintaining proper phosphatidylethanolamine homeostasis in neurons.In this review,we summarize the current knowledge of phosphatidylethanolamine metabolism and its role in neuronal function with a special emphasis on the phosphatidylethanolamine biosynthetic pathway in mitochondria.We then review findings on how phosphatidylethanolamine biosynthesis is affected in major neurodegenerative diseases.Finally,we highlight promising future research areas that will help advance the understanding of neuronal phosphatidylethanolamine mechanisms and identify phosphatidylethanolamine-targeted therapeutic strategies for combating such brain diseases.展开更多
Cochlear hair cell(HC)damage is a primary cause of sensorineural hearing loss.In this study,we performed metabolomic profiling of cochlear sensory epithelium following neomycin-induced HC injury and identified elevate...Cochlear hair cell(HC)damage is a primary cause of sensorineural hearing loss.In this study,we performed metabolomic profiling of cochlear sensory epithelium following neomycin-induced HC injury and identified elevated arginine metabolism as a key metabolic characteristic of damaged HCs.Using a highly sensitive and specific biosensor,we confirmed that injury induced an increase in arginine levels within cochlear HCs.By manipulating the levels of arginine and its downstream metabolites,we discovered that unmetabolized arginine exerts a strong protective effect on cochlear HCs,independent of its downstream metabolites,such as nitric oxide.Furthermore,integrated metabolomic and transcriptomic analyses revealed that arginine plays a critical role in reprogramming phospholipid metabolism.Arginine supplementation enhanced membrane phospholipid saturation through the Lands cycle and de novo lipogenesis,and protected HCs from phospholipid peroxidation-induced membrane damage and subsequent cell death.Notably,arginine supplementation protected hearing from both noise-and aminoglycoside-induced injury in mice.These findings underscore the role of unmetabolized arginine in modulating phospholipid metabolism and preventing membrane damage in cochlear HCs,highlighting that targeting phospholipid metabolism is an effective hearing protection strategy.展开更多
Although human milk fat substitute(HMFS)has been wildly applied in infant formula(IF),there are still some differences in fat composition between human milk and IF,which is extremely attributed to the phospholipid com...Although human milk fat substitute(HMFS)has been wildly applied in infant formula(IF),there are still some differences in fat composition between human milk and IF,which is extremely attributed to the phospholipid composition.We therefore designed a human milk phospholipid substitute(HMPS),and investigated its nutritional outcomes on brain development using C57BL/6J mice.Results showed that HMPS improved mice's cognitive behavior and dendritic development compared to soybean phospholipids and nophospholipid diets.Based on the lipidomics,we revealed that these beneficial outcomes were potentially associated with the increased biosynthesis of N-acylethanolamines,phosphatidylethanolamine(PE),and ether PE,and the decreased metabolism of diacylglycerol and hexosylceramide in brain.It was further found in Kyoto Encyclopedia of Genes and Genomes analysis that glycerophospholipid metabolic pathway participated in the improvement of HMPS on mice's neurodevelopment.In conclusion,this study demonstrated that HMPS improves mice's neurodevelopment,and the glycerophospholipid metabolic pathway plays a major role in this beneficial result,and provided evidence for future application of HMPS in commercial IF.展开更多
Phospholipids have the characteristics of excellent biocompatibility and a especial amphiphilicity.These unique properties make phospholipids most appropriate to be employed as important pharmaceutical excipients and ...Phospholipids have the characteristics of excellent biocompatibility and a especial amphiphilicity.These unique properties make phospholipids most appropriate to be employed as important pharmaceutical excipients and they have a very wide range of applications in drug delivery systems.The aim of this review is to summarize phospholipids and some of their related applications in drug delivery systems,and highlight the relationship between the properties and applications,and the effect of the species of phospholipids on the efficiency of drug delivery.We refer to some relevant literatures,starting from the structures,main sources and properties of phospholipids to introduce their applications in drug delivery systems.The present article focuses on introducing five types of carriers based on phospholipids,including liposomes,intravenous lipid emulsions,micelles,drug-phospholipids complexes and cochleates.展开更多
文摘Nonalcoholic fatty liver disease,recently termed metabolic dysfunction-associated steatotic liver disease,affects 25%of adults globally,with a prevalence reaching 93%in obese individuals.The MANPOWER study,a post hoc analysis of 2843 Russian patients with newly diagnosed nonalcoholic fatty liver disease,evaluated Essentiale Forte N®[essential phospholipids(EPLs)]therapy and a liver enzymebased staging algorithm.Using generalized linear regression and McNemar tests,EPLs reduced liver enzyme levels(alanine aminotransferase:-20.4 U/L,aspartate aminotransferase:-16.9 U/L,gamma-glutamyl transferase:-17.1 U/L at 24 weeks,P<0.001)and improved ultrasonography findings(76.8%reduction in hyperechogenicity,P<0.001).A logistic regression algorithm using alanine aminotransferase,aspartate aminotransferase,and gamma-glutamyl transferase levels achieved 72.3%accuracy,75.6%sensitivity,71.0%specificity,and an area under the receiver operating characteristic curve of 0.74(95%confidence interval:0.71-0.77)for identifying nonalcoholic steatohepatitis.These findings advocate EPLs as a safe,effective therapy and propose a scalable diagnostic tool,urging validation to reduce the reliance on biopsy.
文摘BACKGROUND Since non-alcoholic fatty liver disease(NAFLD)is associated with abnormal liver function tests,treatment recommendations aim to reduce the level of known markers of liver inflammation,such as alanine transaminase(ALT),aspartate transaminase(AST)and gamma-glutamyl transferase(GGT).Essential phospholipids(EPLs)have been shown to reduce levels of these liver enzymes and improve ultrasonographic features.While non-invasive diagnostic tests have been developed to stage inflammation,these tests were not specifically designed to evaluate patients with NAFLD.This highlights the need to describe the liver enzyme profile across the different levels of NAFLD severity for improved grading and staging of NAFLD.AIM To describe liver enzyme profiles across NAFLD severity to inform a diagnostic staging algorithm and identify who may benefit from EPLs.METHODS This post-hoc analysis of the observational MANPOWER study included 2843 adult patients with newly diagnosed NAFLD.The primary endpoint was assessment of baseline liver enzyme profiles.Secondary endpoints were effectiveness of Essentiale®(an EPL)on liver enzyme levels and ultrasonography findings across three definitions of NAFLD:(1)Statistical distribution of liver enzyme levels;(2)MANPOWER cut-offs;and(3)Presence of physiciandiagnosed non-alcoholic steatohepatitis.The best performing algorithm was used to describe the risk factors and profiles associated with increased liver enzyme levels.RESULTS Of the 2843 patients included in this post-hoc analysis,most were female(62.2%),with a mean age of 48.4 years(SD 8.59 years).Overall,mean levels of ALT,AST and GGT increased with NAFLD severity for all three subgroups,with the rate of chronic comorbidities correlated with NAFLD severity.Across each subgroup of interest,Essentiale significantly reduced average liver enzyme levels and improved ultrasonography features,including diffuse liver hyperechogenicity and heterogeneous liver structure(P<0.05),with greater benefit associated with increased severity.Compared with all algorithms tested,the algorithm based on the statistical distribution of liver enzymes displayed the highest accuracy,sensitivity and specificity for the grading and staging of NAFLD and could form the basis of a diagnostic algorithm.CONCLUSION Liver enzyme profiles may identify NAFLD severity and allow monitoring of therapeutic response.Essentiale may improve liver enzyme levels and ultrasonography features.An algorithm could aid in the diagnosis/staging of NAFLD.
文摘Liposomes were prepared with natural soybean phospholipids by extrusion method after rotating-film evaporating technique. Transmission electron micrography was used to detect the appearances of the prepared liposomes, and the liposome diameter was also measured. The prepared liposomes were sphere in shape with the mean diameter of 217 nm and span of 0.838. The phospholipid bilayer structure, suitable for entrapping various effector molecules, could be seen clearly under transmission electron microscopy. The bile salts of sodium cholate and sodium deoxycholate were used as the surfactants to investigate their interaction with liposomes. The turbidities for the mixture of bile salts and liposomes were evaluated by the visible spectrometry method at the wavelength of 500 nm. And the diameter changes of liposomes were also tested to examine the effect of bile salts on liposomes. At the beginning, the diameters and turbidities of liposomes increased a little as the result of mixed micelles formation during the different stages for the structure changes of surfactant-liposomes micelles. The further added bile salts decreased the diameters and turbidities of liposomes. The liposome suspension underwent several rearrangements before small mixed micelles formed. And the diameter of liposomes changed regularly. The interaction of bile salts and liposomes is important for the further study of the behaviors of liposomes in vivo. The drug loaded and release properties of liposomes can also be well reflected by the interaction of liposomes and surfactants.
基金Supported by National Natural Science foundation of China(30670260,3094007)~~
文摘[Objective] The research aimed to determine the existence of free phospholipids in the plasma of three species of freshwater fish and lay the foundation for discussing the physiological mechanism of coagulation phenomena in three species of freshwater fish.[Method] The activity of heated phospholipids was detected by the availability test of heated rabbit cephalin.Small amount of the platelet-poor plasma of the rabbit Oryctolagus cuniculus,the cell-free plasma of the carp Cyprinus carpio,the crucian Carassi...
基金supported by the National Institutes of Health(grant numbers R01NS089737,RF1NS130881,and R21AG089974,to QC).
文摘Phosphatidylethanolamine is a major phospholipid class abundant in the brain,particularly in the inner leaflet of the plasma and mitochondrial membranes.Although it is primarily synthesized from phosphatidylserine via decarboxylation in mitochondria or from ethanolamine via the cytidine diphosphate-ethanolamine pathway in the endoplasmic reticulum,phosphatidylethanolamine that resides in mitochondria is preferentially produced locally and is distinct and separate from the pool of phosphatidylethanolamine made in the endoplasmic reticulum.Mitochondria-derived phosphatidylethanolamine is not only essential for mitochondrial integrity but also is exported to other organelles to fulfill diverse cellular functions.Neurons are highly enriched with phosphatidylethanolamine,and the importance of phosphatidylethanolamine metabolism in neuronal health has recently been recognized following its reported links to Alzheimer’s disease,Parkinson’s disease,and hereditary spastic paraplegia,among other neurological disorders.Indeed,disturbances in mitochondrial function and phosphatidylethanolamine metabolism and the resulting neuronal dysfunction are the common features of individuals suffering from these diseases,highlighting the great importance of maintaining proper phosphatidylethanolamine homeostasis in neurons.In this review,we summarize the current knowledge of phosphatidylethanolamine metabolism and its role in neuronal function with a special emphasis on the phosphatidylethanolamine biosynthetic pathway in mitochondria.We then review findings on how phosphatidylethanolamine biosynthesis is affected in major neurodegenerative diseases.Finally,we highlight promising future research areas that will help advance the understanding of neuronal phosphatidylethanolamine mechanisms and identify phosphatidylethanolamine-targeted therapeutic strategies for combating such brain diseases.
基金supported by the National Natural Science Foundation of China(82271159,82425018,82071049,81830029,82192860,81922018,82201283,82101219,and 82192861)Shanghai Clinical Medical Research Center for Otolaryngology Diseases(20MC1920200)the STI2030-Major Projects(2022ZD0205400).
文摘Cochlear hair cell(HC)damage is a primary cause of sensorineural hearing loss.In this study,we performed metabolomic profiling of cochlear sensory epithelium following neomycin-induced HC injury and identified elevated arginine metabolism as a key metabolic characteristic of damaged HCs.Using a highly sensitive and specific biosensor,we confirmed that injury induced an increase in arginine levels within cochlear HCs.By manipulating the levels of arginine and its downstream metabolites,we discovered that unmetabolized arginine exerts a strong protective effect on cochlear HCs,independent of its downstream metabolites,such as nitric oxide.Furthermore,integrated metabolomic and transcriptomic analyses revealed that arginine plays a critical role in reprogramming phospholipid metabolism.Arginine supplementation enhanced membrane phospholipid saturation through the Lands cycle and de novo lipogenesis,and protected HCs from phospholipid peroxidation-induced membrane damage and subsequent cell death.Notably,arginine supplementation protected hearing from both noise-and aminoglycoside-induced injury in mice.These findings underscore the role of unmetabolized arginine in modulating phospholipid metabolism and preventing membrane damage in cochlear HCs,highlighting that targeting phospholipid metabolism is an effective hearing protection strategy.
基金supported by Huhhot Science&Technology Plan(2021-National Center of Technology innovation for Dairy-4)Innovation Consortium Project(2023RC Consortium-7)+3 种基金National Key Research and Development Program(2023YFF1104502)Ganpo Juncai supports the plan(20232BCJ22046)Nanchang University Jiangxi Financial Science and Technology Special Project(ZBG20230418011)Free Exploration Project of State Key Laboratory(SKLF-ZZB-202317).
文摘Although human milk fat substitute(HMFS)has been wildly applied in infant formula(IF),there are still some differences in fat composition between human milk and IF,which is extremely attributed to the phospholipid composition.We therefore designed a human milk phospholipid substitute(HMPS),and investigated its nutritional outcomes on brain development using C57BL/6J mice.Results showed that HMPS improved mice's cognitive behavior and dendritic development compared to soybean phospholipids and nophospholipid diets.Based on the lipidomics,we revealed that these beneficial outcomes were potentially associated with the increased biosynthesis of N-acylethanolamines,phosphatidylethanolamine(PE),and ether PE,and the decreased metabolism of diacylglycerol and hexosylceramide in brain.It was further found in Kyoto Encyclopedia of Genes and Genomes analysis that glycerophospholipid metabolic pathway participated in the improvement of HMPS on mice's neurodevelopment.In conclusion,this study demonstrated that HMPS improves mice's neurodevelopment,and the glycerophospholipid metabolic pathway plays a major role in this beneficial result,and provided evidence for future application of HMPS in commercial IF.
文摘Phospholipids have the characteristics of excellent biocompatibility and a especial amphiphilicity.These unique properties make phospholipids most appropriate to be employed as important pharmaceutical excipients and they have a very wide range of applications in drug delivery systems.The aim of this review is to summarize phospholipids and some of their related applications in drug delivery systems,and highlight the relationship between the properties and applications,and the effect of the species of phospholipids on the efficiency of drug delivery.We refer to some relevant literatures,starting from the structures,main sources and properties of phospholipids to introduce their applications in drug delivery systems.The present article focuses on introducing five types of carriers based on phospholipids,including liposomes,intravenous lipid emulsions,micelles,drug-phospholipids complexes and cochleates.
