Sugars are widely recognized for their ability to stabilize cell membranes during dehydration.However,the precise mechanisms by which sugars interact with lipid bilayers remain unclear.This mini-review synthesizes fou...Sugars are widely recognized for their ability to stabilize cell membranes during dehydration.However,the precise mechanisms by which sugars interact with lipid bilayers remain unclear.This mini-review synthesizes four key hypotheses explaining sugar-mediated protection of dehydrated bilayers:the Water Replacement Hypothesis(WRH),Hydration Force Hypothesis(HFH),Headgroup Bridging Hypothesis(HBH),and Vitrification Hypothesis(VH).We argue that these mechanisms are not mutually exclusive but instead operate synergistically under different cellular contexts.We propose that these hypotheses are not mutually exclusive but likely operate under different cellular contexts.Future studies should prioritize the development of biologically realistic membrane models-incorporating diverse lipids,proteins,and asymmetric leaflets-to elucidate the exact roles and mechanisms of sugars in membrane stabilization.Such advancements will enhance our understanding of anhydrobiosis and inform cryopreservation strategies for mammalian cells.展开更多
Cancer Stem Cells(CSCs)are cancer cells with self-renewal and tumorigenesis abilities.CSCs in tumor tissues are the leading cause of tumor progression,recurrence,and drug resistance.CSCs have distinct metabolic featur...Cancer Stem Cells(CSCs)are cancer cells with self-renewal and tumorigenesis abilities.CSCs in tumor tissues are the leading cause of tumor progression,recurrence,and drug resistance.CSCs have distinct metabolic features that contribute to maintaining their self-renewal and stemness.Phospholipids are essential components of cell membranes and play fundamental roles in cellular activities.CSCs have abnormal phospholipid metabolism,which affects their self-renewal,differentiation,invasion,and drug resistance.Compared with non-CSCs,the phospholipid metabolism of CSCs mainly focused on significantly increased fatty acid(FAs)and phospholipids synthesis,phospho-lipid unsaturation,and lipolysis-fatty acid oxidation(FAO).In brief,FA and phospholipid metabolism in the anabolic and catabolic pathways are strictly regulated in CSCs to maintain self-renewal and stemness activity.In this review,we summarize the alterations in phospholipid metabolism in CSCs and their impacts on the stemness of CSCs,and we put forward the potential applications of targeting phospholipid metabolism for CSCs,to provide directions for the development of drugs targeting the phospholipid metabolism.展开更多
Developing novel anti-infective drugs is essential to combat antimicrobial resistance,address emerging pathogens,and safeguard global health against evolving infectious threats.A recent publication in the esteemed jou...Developing novel anti-infective drugs is essential to combat antimicrobial resistance,address emerging pathogens,and safeguard global health against evolving infectious threats.A recent publication in the esteemed journal Nature by Qisen Deng et al.reported on the comprehensive evaluation of the therapeutic efficacy of mandimycin against multidrug-resistant(MDR)fungal pathogens.The polyene macrolide antifungal antibiotic,mandimycin,was discovered using a phylogeny-guided natural-product discovery platform.Authors utilized various in vivo mouse models such as systemic and soft-tissue infections to assess the antifungal activity of mandimycin.The efficacy was measured by quantifying the fungal burden in major organs and assessing survival rates.In systemic infections,mandimycin demonstrated significant dose-dependent antifungal efficacy,as compared to amphotericin B,particularly in cases where the latter was ineffective against MDR C.auris.Furthermore,mandimycin showed a favorable safety profile,with low toxicity and no observed side effects at effective doses.The study's findings contribute valuable insights into the potential of mandimycin as a novel antifungal agent,offering hope for improved treatment options against challenging fungal infections.The results pave the way for further research and clinical applications in the fight against antifungal resistance.展开更多
Hearing relies on the structural and functional integrity of cochlear hair cells,particularly their apical F-actin-filled stereocilia.Phospholipid scramblases are important for maintaining membrane asymmetry,but their...Hearing relies on the structural and functional integrity of cochlear hair cells,particularly their apical F-actin-filled stereocilia.Phospholipid scramblases are important for maintaining membrane asymmetry,but their roles in the stereocilia and auditory functions are not fully understood.Here,we identify Plscr5 as a downstream target of the transcription factor POU4F3 essential for hair cell function,whose mutation causes human DFNA15 deafness.Plscr5 knockout mice exhibit progressive hearing loss due to stereocilia degeneration and hair cell loss.Functional analyses reveal that PLSCR5 contributes to phosphatidylserine externalization in hair cell apical membranes,particularly in inner hair cells,and is important for outer hair cell and stereocilia maintenance.Our findings highlight PLSCR5 as an important downstream effector of POU4F3 and regulator of phosphatidylserine externalization and membrane dynamics required for auditory functions.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
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
The concurrence of primary sclerosing cholangitis(PSC)and inflammatory bowel disease(IBD)presents a therapeutic challenge,often necessitating liver transplantation in severe cases.Paeoniflorin(PAE),known for its immun...The concurrence of primary sclerosing cholangitis(PSC)and inflammatory bowel disease(IBD)presents a therapeutic challenge,often necessitating liver transplantation in severe cases.Paeoniflorin(PAE),known for its immunomodulatory and anti-inflammatory properties but with very high-water solubility and low permeability,is formulated into a paeoniflorin/phospholipid complex microemulsion(PAE-ME)to enhance its delivery in this study.It demonstrated the PAE-ME's macrophage-regulating ability to repolarize the pro-inflammatory M1 subtype to the anti-inflammatory M2 type and reduce inflammatory cytokine release.In a PSC-IBD mouse model,PAE-ME alleviated the symptoms and regulated bile acid balance.Given the close connection and crosstalk between the liver and intestine,PAE-ME yielded a synergistic therapeutic effect on both the liver and intestinal lesions.These findings suggest a promising translational approach for complex comorbidities by acting on the liver-gut axis.展开更多
Aim The oxymatrine phospholipid complexs were prepared, and its activity against hepatitis B virus in vitro were studied. Methods Using tetrahydrofuran as a reaction medium, oxymatrine and phospholipids were resolved ...Aim The oxymatrine phospholipid complexs were prepared, and its activity against hepatitis B virus in vitro were studied. Methods Using tetrahydrofuran as a reaction medium, oxymatrine and phospholipids were resolved into the medium, Oxymatrine phospholipid eomplexs were prepared. The toxicity measurements and inhibitory effect on HBsAg, HBeAg, and HBVDNA of oxymatrine phospholipid complex in 2.2.15 cells were studied respectively. Results The content of oxymatrine in the phospholipids eomplexs prepared was 24,86% （W/W）. The TCO of the oxymatrine phospholipid eomplexs was 250 μmol·L^- 1 The inhibitory effect of HBsAg, HBeAg, HBV-DNA of 2.2.15 cells treated by oxymatrine phospholipid complex were higher than those of the oxymatrine. Conclusion Oxymatrine phospholipid complex can have stronger effective activity against hepatitis B virus compared with oxymatrine. So oxymatrine phospholipid eomplexs were showing its potential antiviral activity in hepatitis B treatment.展开更多
Previous study has shown that 10-hydroxycamptothecin（HCPT） has well-established pharmacological effects in vitro.However,its in vivo bioavailability is very poor due to various problems,which severely restricts its ...Previous study has shown that 10-hydroxycamptothecin（HCPT） has well-established pharmacological effects in vitro.However,its in vivo bioavailability is very poor due to various problems,which severely restricts its clinical applications.In the present study,phospholipid complex（PC） technology was employed to improve the solubility and bioavailability of HCPT.XRD data confirmed the formation of HCPT-PC.However,our previously prepared HCPT-PC is too sticky,which may result in the slow dissolution rate and negative effects on its absorption.Therefore,we prepared HCPT-PC-solid dispersion（HCPT-PC-SD）and lipid-based formulations of HCPT-PC through simple preparation process.The results showed that the dissolution rate of HCPT-PC was effectively improved by solid dispersion technology,which reached 91.73%in 45 min.Pharmacokinetic study revealed that the AUC_（0-t） of HCPT-PC-SD and HCPT-PC lipid-based formulations was effectively further increased compared with HCPT-PC.Moreover,we found that the combination of SD technology and lipid-base formulations could be a promising drug-delivery system to improve the oral bioavailability of HCPT-PC.In addition,we showed that the bioavailability of HCPT-PC lipid-base formulations was even greater than that of HCPT-PC-SD.In particular,lipid-base formulations could be prepared just by a simple method,suggesting its feasibility of industrialization.展开更多
The interaction of cisplatin and its analogues with phospholipid molecules of hu-man erythrocyte membranes was studied using IR and ￣31 P NMR methods. Dramatic changes were ob-served at 1300～953 cm￣-1 frequency reg...The interaction of cisplatin and its analogues with phospholipid molecules of hu-man erythrocyte membranes was studied using IR and ￣31 P NMR methods. Dramatic changes were ob-served at 1300～953 cm￣-1 frequency region on the IR spectra .Based on the IR data analysis, it was speculated that the Pt(II) complexes interacted mainly with the polar head groups of phospholipids through electrostatic interaction and certain coordination patterns. The 1 2 h dynamic experiment showed that a recoverable process occurred in case of cis-DCDP and an unrecoverable one for other pt(II)analogues.A similar conclusion could be obtained from￣31 P NMR experimental results.The di-versity was discussed.展开更多
Phospholipids are a major kind of lipids in rice grains and have fundamental nutritional andfunctional benefits to the plant. Their lyso forms （lysophospholipids, LPLs） often form inclusion complexeswith amylose or ...Phospholipids are a major kind of lipids in rice grains and have fundamental nutritional andfunctional benefits to the plant. Their lyso forms （lysophospholipids, LPLs） often form inclusion complexeswith amylose or independently influence the physicochemical and functional properties of rice starch.However, the genetic basis for LPL synthesis in rice endosperm is largely unknown. Here, we performeda preliminary association test of 13 LPL compositions among 20 rice accessions, and identified 22putative main-effect quantitative trait loci responsible for all LPLs except for LPC14：0 and LPE14：0. Fivederived cleaved amplified polymorphic sequences and one insertion/deletion marker for threeLPL-synthesis-related candidate genes were developed. Association analysis revealed two markerssignificantly associated with starch LPL traits. These results provide an insight into the genetic basis ofphospholipid biosynthesis in rice and may contribute to the rice quality breeding programs usingfunctional markers.展开更多
Objective： This article provides an overview of characteristics of phospholipids, the characteristics and influential factors of liposome and microemulsion as carriers for skin delivery of drugs, and the latest advan...Objective： This article provides an overview of characteristics of phospholipids, the characteristics and influential factors of liposome and microemulsion as carriers for skin delivery of drugs, and the latest advances of the phospholipids carriers in transdermal delivery systems. The perspective is that phospholipids carriers may be capable of a wide range of applications in the transdermal delivery system.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
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
In the present study, we developed a novel open-tubular capillary dectrochromatographic method using avidin-phospholipid vesicle complex as the stationary phase for chiral separation of mexiletine hydrochloride. The a...In the present study, we developed a novel open-tubular capillary dectrochromatographic method using avidin-phospholipid vesicle complex as the stationary phase for chiral separation of mexiletine hydrochloride. The avidin immobilized on the phospholipid vesicle consisting of 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine （DPPE） and L-u-phosphatidyl-L-serine （PS） （80：20, mg%） was coated in the capillary. The homogeneity and separation performance of the coating were evaluated in terms o f phospholipid vesicle characterization and the resolution of D,L-Tryptophan. As for mexiletine hydrochloride, four vital parameters affecting the separation efficiency of coating capillary, including buffer type, buffer pH, buffer concentration and the applied voltage, were studied in detail. Under the optimum conditions, the enantiomers could be separated well with good resolution. All the satisfactory results indicated that this method using avidin-phospholipid vesicle complex as the stationary phase was suitable and feasible, which had great potential in pharmaceutical separation Of enantiomers.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
Objective To evaluate the alterations of biomarkers in the development and progression of coal workers＇ pneumoconiosis （CWP）. Methods The type and number of cells, and the levels of tumor necrosis factor-alpha （T...Objective To evaluate the alterations of biomarkers in the development and progression of coal workers＇ pneumoconiosis （CWP）. Methods The type and number of cells, and the levels of tumor necrosis factor-alpha （TNF-α）, pulmonary surfactant protein, phospholipids and fibronectin in bronchoalveolar lavage fluid were assayed in 14 health active coal miners, 21 coal miners without CWP and 13 miners with CWP of 0/1 to 1/1. Results Compared to active coal miners without CWP （8,23μg/mL）, TNF-α concentration was gradually decreased when dust exposure was stopped （5.90 μg/mL）. Elevated surfactant protein A （SP-A） level and phosphatidylglycerol （PG） to phosphatidylinositol （PI） ratio were found in miners actively exposed to coal dust （6528 μg/mL for SP-A and 10. for PG/P1）, and both parameters decreased when CWP progressed from CWP （0/1） （3419μg/mL for SP-A and 5.9 for PG/PI） to CWP （1/1） （1654 μg/mL for SP-A and 5.5 for PG/PI）. Conclusion Biomarkers in bronchoalveolar lavage fluid can be used to screen coal miners at high risk of developing coal workers＇ pneumoconiosis.展开更多
The phospholipid fatty acid （PLFA） composition was analyzed in two red soils experimentally contaminated with copper at different concentrations. The total amounts ofphospholipid fatty acids （PLFAs） in both red so...The phospholipid fatty acid （PLFA） composition was analyzed in two red soils experimentally contaminated with copper at different concentrations. The total amounts ofphospholipid fatty acids （PLFAs） in both red soils were significantly correlated with soil microbial biomass C and N, which decreased consistently with increasing levels of copper. The relative quantities of the PLFAs 17：0 （10 Me）, i16：0, il 5：0 and 16：1w5c, decreased with increasing heavy metal concentration, while those of cyl7：0, which is an indicator of gram-negative bacteria, increased. The Shannon index calculated from the PLFA data indicated that Cu addition in the red soils decreased the population diversity of soil microbial communities. Multivariate analysis of PLFA data demonstrated that high levels of Cu application had a significant impact on microbial community structure and there is a threshold metal concentration for PLFA composition. Comparatively higher toxic effect on microbial biomass and community structure were found in the red sandy soil than those in the red clayey soil. The differential effect of Cu addition on microbial communities in the two soils may be due to differences in soil texture and cation exchange capacity.展开更多
Analysis of phospholipid fatty acids (PLFAs) was used to estimate the microbial community structures of eight Chinese red soils with different fertility levels and land use histories. The total amounts of PLFAs in the...Analysis of phospholipid fatty acids (PLFAs) was used to estimate the microbial community structures of eight Chinese red soils with different fertility levels and land use histories. The total amounts of PLFAs in the soils were significantly correlated with soil organic carbon, total nitrogen, microbial biomass C and basal respiration, indicating that total PLFA was closely related to fertility and sustainability in these highly weathered soils. Soils for the eroded wasteland were rich in Gram-positive species. When the eroded soils were planted with citrus trees, the soil microbial population had changed little in 4 years but took up to 8-12 years before it reached a significantly different population. Multivariate analysis of PLFAs demonstrated that land use history and plant cover type had a significant impact on microbial community structure. However, the difference of soil microbial community structure in the paddy field compared to other land uses was not larger than expected in this experiment.展开更多
The bioavailability of docosahexaenoic acid(DHA) and eicosapentaenoic acid(EPA) depends on their chemical forms. This study investigated the long-term effects of DHA-bound triglyceride(TG-DHA), DHA-bound phospholipid(...The bioavailability of docosahexaenoic acid(DHA) and eicosapentaenoic acid(EPA) depends on their chemical forms. This study investigated the long-term effects of DHA-bound triglyceride(TG-DHA), DHA-bound phospholipid(PL-DHA), and the combination of TG-DHA and egg yolk phospholipid(Egg-PL) on lipid metabolism in mice fed with a high-fat diet(fat levels of 22.5%). Male C57BL/6J mice were fed with different formulations containing 0.5% DHA, including TG-DHA, PL-DHA, and the combination of TG-DHA and Egg-PL, for 6 weeks. Serum, hepatic, and cerebral lipid concentrations and the fatty acid compositions of the liver and brain were determined. The concentrations of serum total triglyceride(TG), total cholesterol(TC), high-density lipoprotein cholesterol(HDL-c), and hepatic TG in the PL-DHA group and the combination group were significantly lower than those in the high-fat(HF) group(P < 0.05). Atherogenic index(AI) of the PL-DHA group was significantly lower than that of the combination group(P < 0.05). Hepatic TC level in the combination group was significantly lower than that in the HF group(P < 0.05), but no significant difference was observed between the combination group and the PL-DHA group. Both the PL-DHA and the combination groups showed significantly increased DHA levels in the liver compared with the HF group(P < 0.05). However, there were no obvious increases in the cerebral DHA levels in all DHA diet groups. These results suggest that PL-DHA was superior to the combination of TG-DHA and Egg-PL in decreasing the AI. Long-term dietary supplementation with low amount of DHA(0.5%) may improve hepatic DHA levels, although cerebral DHA levels may not be enhanced.展开更多
基金supported by the National Natural Science Foundation of China,China(Grant No.52376052)the Anhui Provincial Natural Science Foundation,China(Grant No.2308085ME174).
文摘Sugars are widely recognized for their ability to stabilize cell membranes during dehydration.However,the precise mechanisms by which sugars interact with lipid bilayers remain unclear.This mini-review synthesizes four key hypotheses explaining sugar-mediated protection of dehydrated bilayers:the Water Replacement Hypothesis(WRH),Hydration Force Hypothesis(HFH),Headgroup Bridging Hypothesis(HBH),and Vitrification Hypothesis(VH).We argue that these mechanisms are not mutually exclusive but instead operate synergistically under different cellular contexts.We propose that these hypotheses are not mutually exclusive but likely operate under different cellular contexts.Future studies should prioritize the development of biologically realistic membrane models-incorporating diverse lipids,proteins,and asymmetric leaflets-to elucidate the exact roles and mechanisms of sugars in membrane stabilization.Such advancements will enhance our understanding of anhydrobiosis and inform cryopreservation strategies for mammalian cells.
基金supported by grants from National Natural Science Foundation of China(81902784,81771086)by the Fund of Sichuan Provincial Department of science and technology(2024YFFK0393,2022YFS0039)+1 种基金the Research and Develop Program,West China Hospital of Stomatology,Sichuan University(LCYJ2023-DL-2,RD-02-202002)the CAMS Innovation Fund for Medical Sciences(CIFMS,2019-I2M-5-004)。
文摘Cancer Stem Cells(CSCs)are cancer cells with self-renewal and tumorigenesis abilities.CSCs in tumor tissues are the leading cause of tumor progression,recurrence,and drug resistance.CSCs have distinct metabolic features that contribute to maintaining their self-renewal and stemness.Phospholipids are essential components of cell membranes and play fundamental roles in cellular activities.CSCs have abnormal phospholipid metabolism,which affects their self-renewal,differentiation,invasion,and drug resistance.Compared with non-CSCs,the phospholipid metabolism of CSCs mainly focused on significantly increased fatty acid(FAs)and phospholipids synthesis,phospho-lipid unsaturation,and lipolysis-fatty acid oxidation(FAO).In brief,FA and phospholipid metabolism in the anabolic and catabolic pathways are strictly regulated in CSCs to maintain self-renewal and stemness activity.In this review,we summarize the alterations in phospholipid metabolism in CSCs and their impacts on the stemness of CSCs,and we put forward the potential applications of targeting phospholipid metabolism for CSCs,to provide directions for the development of drugs targeting the phospholipid metabolism.
基金the National Key Research and Development Program of China(2023YFD1700500)the College Student Research Training Program(202110307002T)Bayer Grants4Ag Initiative for their support.
文摘Developing novel anti-infective drugs is essential to combat antimicrobial resistance,address emerging pathogens,and safeguard global health against evolving infectious threats.A recent publication in the esteemed journal Nature by Qisen Deng et al.reported on the comprehensive evaluation of the therapeutic efficacy of mandimycin against multidrug-resistant(MDR)fungal pathogens.The polyene macrolide antifungal antibiotic,mandimycin,was discovered using a phylogeny-guided natural-product discovery platform.Authors utilized various in vivo mouse models such as systemic and soft-tissue infections to assess the antifungal activity of mandimycin.The efficacy was measured by quantifying the fungal burden in major organs and assessing survival rates.In systemic infections,mandimycin demonstrated significant dose-dependent antifungal efficacy,as compared to amphotericin B,particularly in cases where the latter was ineffective against MDR C.auris.Furthermore,mandimycin showed a favorable safety profile,with low toxicity and no observed side effects at effective doses.The study's findings contribute valuable insights into the potential of mandimycin as a novel antifungal agent,offering hope for improved treatment options against challenging fungal infections.The results pave the way for further research and clinical applications in the fight against antifungal resistance.
基金supported by the National Natural Science Foundation of China(82171136 and 92368110 to G.W.,82201291 to G.-J.Z.,82192861 to Z.X.,81970884 and 82192862 to X.G.)the Natural Science Foundation of Jiangsu Province(BK20220188 to Q.L.,BK20220189 to G.-J.Z.)the Fundamental Research Funds for the Central Universities(021414380533 to G.W.).
文摘Hearing relies on the structural and functional integrity of cochlear hair cells,particularly their apical F-actin-filled stereocilia.Phospholipid scramblases are important for maintaining membrane asymmetry,but their roles in the stereocilia and auditory functions are not fully understood.Here,we identify Plscr5 as a downstream target of the transcription factor POU4F3 essential for hair cell function,whose mutation causes human DFNA15 deafness.Plscr5 knockout mice exhibit progressive hearing loss due to stereocilia degeneration and hair cell loss.Functional analyses reveal that PLSCR5 contributes to phosphatidylserine externalization in hair cell apical membranes,particularly in inner hair cells,and is important for outer hair cell and stereocilia maintenance.Our findings highlight PLSCR5 as an important downstream effector of POU4F3 and regulator of phosphatidylserine externalization and membrane dynamics required for auditory functions.
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.
基金National Key Research and Development Program of China(No.2022YFE0203600,China)National Natural Science Foundation of China(Nos.82341232,81925035)+3 种基金Department of Science and Technology of Guangdong Province(No.2021B0909050003)Chinese Academy of Sciences President's International Fellowship Initiative(No.2024VBB0004)the Scientific Innovation Group Project in Zhongshan(No.CXTD2022011)supported by grants from the Program of Shanghai Committee of Science and Technology,China(No.22S21902900)。
文摘The concurrence of primary sclerosing cholangitis(PSC)and inflammatory bowel disease(IBD)presents a therapeutic challenge,often necessitating liver transplantation in severe cases.Paeoniflorin(PAE),known for its immunomodulatory and anti-inflammatory properties but with very high-water solubility and low permeability,is formulated into a paeoniflorin/phospholipid complex microemulsion(PAE-ME)to enhance its delivery in this study.It demonstrated the PAE-ME's macrophage-regulating ability to repolarize the pro-inflammatory M1 subtype to the anti-inflammatory M2 type and reduce inflammatory cytokine release.In a PSC-IBD mouse model,PAE-ME alleviated the symptoms and regulated bile acid balance.Given the close connection and crosstalk between the liver and intestine,PAE-ME yielded a synergistic therapeutic effect on both the liver and intestinal lesions.These findings suggest a promising translational approach for complex comorbidities by acting on the liver-gut axis.
文摘Aim The oxymatrine phospholipid complexs were prepared, and its activity against hepatitis B virus in vitro were studied. Methods Using tetrahydrofuran as a reaction medium, oxymatrine and phospholipids were resolved into the medium, Oxymatrine phospholipid eomplexs were prepared. The toxicity measurements and inhibitory effect on HBsAg, HBeAg, and HBVDNA of oxymatrine phospholipid complex in 2.2.15 cells were studied respectively. Results The content of oxymatrine in the phospholipids eomplexs prepared was 24,86% （W/W）. The TCO of the oxymatrine phospholipid eomplexs was 250 μmol·L^- 1 The inhibitory effect of HBsAg, HBeAg, HBV-DNA of 2.2.15 cells treated by oxymatrine phospholipid complex were higher than those of the oxymatrine. Conclusion Oxymatrine phospholipid complex can have stronger effective activity against hepatitis B virus compared with oxymatrine. So oxymatrine phospholipid eomplexs were showing its potential antiviral activity in hepatitis B treatment.
基金Science and Technology Department of Henan province Fund Project(Grant No.144300510019)
文摘Previous study has shown that 10-hydroxycamptothecin（HCPT） has well-established pharmacological effects in vitro.However,its in vivo bioavailability is very poor due to various problems,which severely restricts its clinical applications.In the present study,phospholipid complex（PC） technology was employed to improve the solubility and bioavailability of HCPT.XRD data confirmed the formation of HCPT-PC.However,our previously prepared HCPT-PC is too sticky,which may result in the slow dissolution rate and negative effects on its absorption.Therefore,we prepared HCPT-PC-solid dispersion（HCPT-PC-SD）and lipid-based formulations of HCPT-PC through simple preparation process.The results showed that the dissolution rate of HCPT-PC was effectively improved by solid dispersion technology,which reached 91.73%in 45 min.Pharmacokinetic study revealed that the AUC_（0-t） of HCPT-PC-SD and HCPT-PC lipid-based formulations was effectively further increased compared with HCPT-PC.Moreover,we found that the combination of SD technology and lipid-base formulations could be a promising drug-delivery system to improve the oral bioavailability of HCPT-PC.In addition,we showed that the bioavailability of HCPT-PC lipid-base formulations was even greater than that of HCPT-PC-SD.In particular,lipid-base formulations could be prepared just by a simple method,suggesting its feasibility of industrialization.
文摘The interaction of cisplatin and its analogues with phospholipid molecules of hu-man erythrocyte membranes was studied using IR and ￣31 P NMR methods. Dramatic changes were ob-served at 1300～953 cm￣-1 frequency region on the IR spectra .Based on the IR data analysis, it was speculated that the Pt(II) complexes interacted mainly with the polar head groups of phospholipids through electrostatic interaction and certain coordination patterns. The 1 2 h dynamic experiment showed that a recoverable process occurred in case of cis-DCDP and an unrecoverable one for other pt(II)analogues.A similar conclusion could be obtained from￣31 P NMR experimental results.The di-versity was discussed.
基金financially supported by the Fundamental Research Funds for the Central Universities at Zhejiang University,Hangzhou,China(Grant No.2016XZZX001-09)
文摘Phospholipids are a major kind of lipids in rice grains and have fundamental nutritional andfunctional benefits to the plant. Their lyso forms （lysophospholipids, LPLs） often form inclusion complexeswith amylose or independently influence the physicochemical and functional properties of rice starch.However, the genetic basis for LPL synthesis in rice endosperm is largely unknown. Here, we performeda preliminary association test of 13 LPL compositions among 20 rice accessions, and identified 22putative main-effect quantitative trait loci responsible for all LPLs except for LPC14：0 and LPE14：0. Fivederived cleaved amplified polymorphic sequences and one insertion/deletion marker for threeLPL-synthesis-related candidate genes were developed. Association analysis revealed two markerssignificantly associated with starch LPL traits. These results provide an insight into the genetic basis ofphospholipid biosynthesis in rice and may contribute to the rice quality breeding programs usingfunctional markers.
基金This study was supported by Chongqing Tackle Key Prob-lems in Science and Technology Project(CSTC,2006AB5011)
文摘Objective： This article provides an overview of characteristics of phospholipids, the characteristics and influential factors of liposome and microemulsion as carriers for skin delivery of drugs, and the latest advances of the phospholipids carriers in transdermal delivery systems. The perspective is that phospholipids carriers may be capable of a wide range of applications in the transdermal delivery system.
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...
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support of Professor Xuan Zhang’s research group,Laboratory of pharmaceutics,School of Pharmaceutical Sciences,Peking UniversityBeijing Kaiao Technology Development Co.,Ltd.
文摘In the present study, we developed a novel open-tubular capillary dectrochromatographic method using avidin-phospholipid vesicle complex as the stationary phase for chiral separation of mexiletine hydrochloride. The avidin immobilized on the phospholipid vesicle consisting of 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine （DPPE） and L-u-phosphatidyl-L-serine （PS） （80：20, mg%） was coated in the capillary. The homogeneity and separation performance of the coating were evaluated in terms o f phospholipid vesicle characterization and the resolution of D,L-Tryptophan. As for mexiletine hydrochloride, four vital parameters affecting the separation efficiency of coating capillary, including buffer type, buffer pH, buffer concentration and the applied voltage, were studied in detail. Under the optimum conditions, the enantiomers could be separated well with good resolution. All the satisfactory results indicated that this method using avidin-phospholipid vesicle complex as the stationary phase was suitable and feasible, which had great potential in pharmaceutical separation Of enantiomers.
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.
基金This research was supported by University of Essen in Germany and Xishan Coal & Power Company
文摘Objective To evaluate the alterations of biomarkers in the development and progression of coal workers＇ pneumoconiosis （CWP）. Methods The type and number of cells, and the levels of tumor necrosis factor-alpha （TNF-α）, pulmonary surfactant protein, phospholipids and fibronectin in bronchoalveolar lavage fluid were assayed in 14 health active coal miners, 21 coal miners without CWP and 13 miners with CWP of 0/1 to 1/1. Results Compared to active coal miners without CWP （8,23μg/mL）, TNF-α concentration was gradually decreased when dust exposure was stopped （5.90 μg/mL）. Elevated surfactant protein A （SP-A） level and phosphatidylglycerol （PG） to phosphatidylinositol （PI） ratio were found in miners actively exposed to coal dust （6528 μg/mL for SP-A and 10. for PG/P1）, and both parameters decreased when CWP progressed from CWP （0/1） （3419μg/mL for SP-A and 5.9 for PG/PI） to CWP （1/1） （1654 μg/mL for SP-A and 5.5 for PG/PI）. Conclusion Biomarkers in bronchoalveolar lavage fluid can be used to screen coal miners at high risk of developing coal workers＇ pneumoconiosis.
基金The National Natural Science Foundation of China (No. 30200164 40371063) and the Foundation for the Retuned Scholars ofZhejiang Province
文摘The phospholipid fatty acid （PLFA） composition was analyzed in two red soils experimentally contaminated with copper at different concentrations. The total amounts ofphospholipid fatty acids （PLFAs） in both red soils were significantly correlated with soil microbial biomass C and N, which decreased consistently with increasing levels of copper. The relative quantities of the PLFAs 17：0 （10 Me）, i16：0, il 5：0 and 16：1w5c, decreased with increasing heavy metal concentration, while those of cyl7：0, which is an indicator of gram-negative bacteria, increased. The Shannon index calculated from the PLFA data indicated that Cu addition in the red soils decreased the population diversity of soil microbial communities. Multivariate analysis of PLFA data demonstrated that high levels of Cu application had a significant impact on microbial community structure and there is a threshold metal concentration for PLFA composition. Comparatively higher toxic effect on microbial biomass and community structure were found in the red sandy soil than those in the red clayey soil. The differential effect of Cu addition on microbial communities in the two soils may be due to differences in soil texture and cation exchange capacity.
基金Project supported by the Science and Technology Development Bureau of European Union (CⅠ1-CT93-0009), by the National Key Basic
文摘Analysis of phospholipid fatty acids (PLFAs) was used to estimate the microbial community structures of eight Chinese red soils with different fertility levels and land use histories. The total amounts of PLFAs in the soils were significantly correlated with soil organic carbon, total nitrogen, microbial biomass C and basal respiration, indicating that total PLFA was closely related to fertility and sustainability in these highly weathered soils. Soils for the eroded wasteland were rich in Gram-positive species. When the eroded soils were planted with citrus trees, the soil microbial population had changed little in 4 years but took up to 8-12 years before it reached a significantly different population. Multivariate analysis of PLFAs demonstrated that land use history and plant cover type had a significant impact on microbial community structure. However, the difference of soil microbial community structure in the paddy field compared to other land uses was not larger than expected in this experiment.
基金supported by the grants from the project supported by the State Key Program of National Natural Science of China (No.31330060)the National Natural Science Foundation of China (Nos.31301446,31371757)the Program for New Century Excellent Talents in University (No.NCET-13-0534)
文摘The bioavailability of docosahexaenoic acid(DHA) and eicosapentaenoic acid(EPA) depends on their chemical forms. This study investigated the long-term effects of DHA-bound triglyceride(TG-DHA), DHA-bound phospholipid(PL-DHA), and the combination of TG-DHA and egg yolk phospholipid(Egg-PL) on lipid metabolism in mice fed with a high-fat diet(fat levels of 22.5%). Male C57BL/6J mice were fed with different formulations containing 0.5% DHA, including TG-DHA, PL-DHA, and the combination of TG-DHA and Egg-PL, for 6 weeks. Serum, hepatic, and cerebral lipid concentrations and the fatty acid compositions of the liver and brain were determined. The concentrations of serum total triglyceride(TG), total cholesterol(TC), high-density lipoprotein cholesterol(HDL-c), and hepatic TG in the PL-DHA group and the combination group were significantly lower than those in the high-fat(HF) group(P < 0.05). Atherogenic index(AI) of the PL-DHA group was significantly lower than that of the combination group(P < 0.05). Hepatic TC level in the combination group was significantly lower than that in the HF group(P < 0.05), but no significant difference was observed between the combination group and the PL-DHA group. Both the PL-DHA and the combination groups showed significantly increased DHA levels in the liver compared with the HF group(P < 0.05). However, there were no obvious increases in the cerebral DHA levels in all DHA diet groups. These results suggest that PL-DHA was superior to the combination of TG-DHA and Egg-PL in decreasing the AI. Long-term dietary supplementation with low amount of DHA(0.5%) may improve hepatic DHA levels, although cerebral DHA levels may not be enhanced.
