ANALYTICAL CHEMISTRY
·
2020
·
IF 6.785
Xue Zhao,Gang Wu,Wenpeng Zhang,Mengqiu Dong,Yu Xia
Sphingomyelins (SMs) are an essential class of lipids widely existing in different organisms. The sphingoid base and N-acyl chain are two building blocks which can undergo different types of modifications during lipogenesis, including desaturation, hydroxylation, and methyl branching. Current lipidomic analysis methods cannot provide detailed information on these structural motifs. Herein, we developed a tandem mass spectrometric method by harnessing radical-directed dissociation (RDD) from collision-induced dissociation (CID) of the bicarbonate anion adduct of SM ([M + HCO3]−). A major RDD channel produced a high-abundance fragment carrying the intact N-acyl chain, termed as “N-acyl fragment”, allowing the assignment of the sphingoid base/N-acyl composition and relative quantitation of compositional isomers of SM at high sensitivity. RDD also produced intrachain fragments in lower abundances, which helped localization of methyl branching and hydroxylation in SM. The acetone Paternò–Büchi (PB) reaction was found to be capable of derivatizing the Δ4 carbon–carbon double bond (C═C) in sphingosine (SPH) base and producing C═C diagnostic ions upon CID, albeit at much lower efficiencies than those of the isolated C═C in alkyl chains. A liquid chromatography–mass spectrometry workflow was developed by incorporating MS2 CID of SM via [M + HCO3]− and PB-MS2 CID. The capability of profiling SM with detailed structural information was demonstrated by analyzing complex lipid extracts from porcine brain and Caenorhabditis elegans. These results provided visualization of the sphingoid base/N-acyl compositional isomers of SM lipids and revealed large structural diversity from each sample. These included identification of the sphingadiene base [d18:1(Δ4,14)], C═C location isomers in N-acyls, C-2 hydroxylation of N-acyls, and iso-methyl branched SPH base.
研究领域:
生物化学
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脂质组学
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分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2025
·
IF 9.8
Chenyu Jiang,Xinghe Zhang,Jiahui Yu,Ling-zhi Cheong,Xingguo Wang,Wei Wei
Herein, polar lipids, including glycerophospholipid, lysophospholipid, cholesterol (CHOL), sphingomyelin (SM), and ceramide (Cer), in human breast milk were subjected to lipidomic analysis via UPSFC-Q-TOF-MS. A total of 11 lipid classes and 195 molecular species were identified and quantified in human breast milk samples ( n = 126) from three lactational stages across three regions in China. CHOL and SM together account for more than 50 % of the total polar lipids. The total polar lipids, SM, and phosphatidylethanolamine (PE) were ∼ 54.5, ∼17.8, and ∼ 3.5 mg/100 mL, respectively, which both significantly ( P < 0.05) increased from colostrum to later lactational stages. DHA is highly enriched (68 % of the total DHA) in PE molecules. SM and Cer contain high ratios of nervonic acid (24:1 n-9), ∼35 % and ∼ 23 %, respectively. General patterns exist in the variation of polar lipid molecular species in human breast milk across different regions throughout the lactational stages.
研究领域:
营养学
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脂质组学
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生物化学
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产品关联
DOI
PubMed
高影响因子
LWT-FOOD SCIENCE AND TECHNOLOGY
·
2021
·
IF 4.952
Wei Wei,Jin Cheng,Jie Yang,Chen Chen,Qingzhe Jin,Jie Song,Xingguo Wang
The nutritional profile of human milk varies significantly during storage, and the impact of storage conditions on phospholipid (PL) composition and fat globule structure is not well studied. This study aimed to investigate the changes in human milk PL composition and human milk fat globule (HMFG) structure during long-term storage, at 4 °C, −20 °C and −80 °C for 30, 60, 90 and 120 days. The PLs in human milk were quantified using 31 P NMR, and the microstructure of HMFG was observed using multi microscopes. After 120 days of storage, the total PLs decreased from 19.1 μmol/100 mL milk to 4.8 μmol/100 mL, 8.2 μmol/100 mL and 10.3 μmol/100 mL at 4 °C, −20 °C and −80 °C, respectively. Glycerophospholipid showed a higher lipolysis rate than sphingomyelin . PLs on milk fat globule membranes degraded during storage, which caused the release of internal triacylglycerols and the flocculation of fat globules at the broken membrane.
研究领域:
营养学
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食品科学
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生物化学
✓ 已验证
产品关联
DOI
高影响因子
Cell Metabolism
·
2025
·
IF 30.9
Jie Jiang,Yuqing Gao,Jiang Wang,Yan Huang,Rong Yang,Yongxin Zhang,Yuandi Ma,Yingquan Wen,Gongkai Luo,Shurui Zhang,Yutang Cao,Minjun Yu,Qinxue Wang,Shulei Hu,Kanglong Wang,Xiaozhen Guo,Frank J. Gonzalez,Yameng Liu,Hong Liu,Qing Xie,Cen Xie
Metabolic-dysfunction-associated steatohepatitis (MASH) remains a major health challenge. Herein, we identify sphingomyelin phosphodiesterase 3 (SMPD3) as a key driver of hepatic ceramide accumulation through increasing sphingomyelin hydrolysis at the cell membrane. Hepatocyte-specific Smpd3 gene disruption or pharmacological inhibition of SMPD3 alleviates MASH, whereas reintroducing SMPD3 reverses the resolution of MASH. Although healthy livers express low-level SMPD3, lipotoxicity-induced DNA damage suppresses sirtuin 1 (SIRT1), triggering an upregulation of SMPD3 during MASH. This disrupts membrane sphingomyelin-ceramide balance and promotes disease progression by enhancing caveolae-dependent lipid uptake and extracellular vesicle secretion from steatotic hepatocytes to exacerbate inflammation and fibrosis. Consequently, SMPD3 acts as a central hub integrating key MASH hallmarks. Notably, we discovered a bifunctional agent that simultaneously activates SIRT1 and inhibits SMPD3, which shows significant therapeutic potential in MASH treatment. These findings suggest that inhibition of hepatic SMPD3 restores membrane sphingolipid metabolism and holds great promise for developing novel MASH therapies.
研究领域:
生物化学
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肝脏病学
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代谢医学
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产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2020
·
IF 6.306
Jiaxin Wang,Xuening Lu,Jiaen Zhang,Zeheng Xiao
Lipids such as phosphatidylcholine (PC), 3- sn -phosphatidylethanolamine (PE), sphingomyelin (SM) and L-α-lysophosphatidylcholine (LPC) are the major components of biological membranes and play important roles in physiological functions. Here, PC, PE, SM, and LPC were extracted from golden apple snails (GAS, Pomacea canaliculata ) and GAS flesh (GASF) using an ethanol/hexane sequential scheme and quantified simultaneously using ultra-high performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UHPLC-ESI-MS/MS) to evaluate whether the GAS could be the source of the four lipids. Our results suggest that ethanol extracts contained the most crude lipids, and the yield of dry (evaporated) lipids were 3.45 g per 100 g fresh GASF and 1.82 g per 100 g of fresh GAS. Quantification of the lipids using UHPLC-ESI-MS/MS suggested that GAS contained PE, PC, SM and LPC, with SM being the most abundant lipid (after purification: 1.71 and 1.42 mg g −1 dry weight from 100 g of GASF and GAS, respectively). The method we used is cost-effective, and the recovery rates of ethanol and hexane ranged from 80−91% and 87−91% respectively. Overall, GAS and GASF are potential raw materials for lipids such as SM and PC extraction using the ethanol/hexane method. Comparatively, lipids extraction from the GAS is more effective and timesaving. Our finding would provide a way to utilize GAS and potentially control its invasion.
研究领域:
生物化学
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分析化学
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入侵生物学
✓ 已验证
DOI
高影响因子
PHYTOMEDICINE
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2024
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IF 6.7
Yonggui Song,Meixizi Lai,Zhou Liao,Zhentao Zhang,Genhua Zhu,Ming Yang,Zhifu Ai,Qin Zheng,Dan Su
Background Since the pathogenesis of depression is complex, antidepressant therapy remains unsatisfactory. Recent evidence suggests a link between depression and lipid metabolism. Saikosaponin (SS) exhibits antidepression and lipid-regulating effects in modern pharmacology. However, it is unknown whether lipid regulation is the key mechanism of the SS antidepressant effect and how it works. Purpose In this study, we investigated the relationship between the antidepressant activity of SS and the regulation of lipid metabolism and explored potential mechanisms. Methods APOE -/- mice, in combination with the chronic unpredictable mild stress (CUMS) model, were used to study the relationship between SS antidepressant activity and lipid metabolism through behavioral, electrophysiological techniques, and non-targeted lipidomics. Western blot, primary cell culture technology, and laser speckle cerebral blood flow imaging were employed to elucidate potential mechanisms. GraphPad Prism was used for statistical analysis, and p < 0.05 was considered statistically significant. Results APOE -/- mice exhibit more severe depressive-like behavior and dysregulation of sphingolipid metabolism in CUMS. SS alleviates depressive behavior and cortical sphingolipid metabolism disorder caused by CUMS, but has no effect on APOE -/- mice. SS alleviates the imbalance between ceramide (Cer) and sphingomyelin (SM) through acidic sphingomyelinase (AMSase). In addition, SS regulates neuronal glutamate release via sphingolipid metabolism, thereby alleviating the CUMS-induced inhibition of neurovascular coupling (regulates metabotropic glutamate receptor and IP3 receptor), which ameliorates the reduction of cerebral blood flow in depressed mice. Conclusion Our study highlights the role of lipid metabolism in the antidepressant activity of SS and explores its underlying mechanisms. This study provided new insights into the better understanding of the antidepressant mechanisms of phytomedicine while increasing the possibility of lipid metabolism as a therapeutic strategy for depression.
研究领域:
药理学
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神经科学
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脂质生物学
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行为科学
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产品关联
DOI
PubMed
高影响因子
Future Medicinal Chemistry
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2017
·Vol. 9
·期 16
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IF 3.556
Kan Yang,Biao Gao,Xianjun Ming,Zhipeng Huang,Minghui Wang,Jibin Dong,Jinxin Wang
Aim: ASM, which hydrolyzes sphingomyelin into ceramide, is recognized as a therapeutic target for UV-induced skin damage. Direct inhibitors for this enzyme are rare. Here we synthesized several series of 1,3,6,7-tetrahydroxy-xanthone derivatives as novel ASM inhibitors. Results: Several compounds were more potent than the lead compound, among which 5b was found competitively inhibiting the enzyme and dose-dependently reducing ceramide generation. Furthermore, 5b and 5c showed excellent protective effect to skin keratinocytes against UV. Quantitative structure–activity relationship investigation revealed detail relationships between molecular structure and biological activity. Insight into the binding mode was precisely illuminated by molecule docking. Conclusion: This work would provide fresh ideas and strong supports for further development of ASM inhibitors and drug candidates for skin damage.
研究领域:
药理学
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皮肤病学
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化学生物学
✓ 已验证
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2024
·
IF 8.5
Yi Wang,Mengyuan Guo,Peipei Wu,Chong Chen,Weibo Zhang,Fazheng Ren,Pengjie Wang,Shouyun Wu,Jianhuan Wei,Jie Luo,Jinghua Yu
This study provides insights into the composition and in-situ structures of the milk fat globule membrane (MFGM) in buffalo milk with different fat globule sizes (0.55 μm and 8.04 μm). Small fat globules contained a higher amount of MFGM proteins and polar lipids, while the content of MFGM components (except for ADPH) was greater per unit membrane area in large fat globules. A total of 386 differentially expressed proteins were identified, with many of the most differentially expressed proteins being associated with human diseases, such as cancer and elderly diseases. The coverage of sphingomyelin and certain MFGM proteins (BTN and PAS 6/7) on large fat globules was higher, potentially linked to the presence of larger, irregular lipid rafts and patch-shaped glycocalyxes, respectively. These findings suggest that small fat globules are suitable for nutritional fortification of buffalo milk, while large fat globules are appropriate for the preparation of functional dairy-based ingredients.
研究领域:
食品科学
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营养学
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生物化学
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蛋白质组学
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脂质组学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2022
·
IF 5.195
Tingting Wang,Yonggui Song,Huanhua Xu,Yali Liu,Hongwei He,Mingyue Zhou,Chen Jin,Ming Yang,Zhifu Ai,Dan Su
Ethnopharmacological relevance Pentacyclic triterpenoid saponin (PTS) is a kind of particular chemicals with various pharmacological activities, as well as surface activity, mucosal irritation and hemolysis. PTS is closely related to the exertion of efficacy or adverse reactions in plant medicines rich in this component. For the better clinical application of natural resources, how to reduce toxicity and enhance curative efficacy is an important problem which needs to be solved at present. Till now, there has been few studies directly investigating the problem. Aim of study Through comparison study of Radix Bupleuri (Chai hu) and Pulsatilla chinensis (Bai tou weng), which are typical traditional Chinese medicines containing PTS, explore the potential change rule of material basis and the mechanism of detoxification and synergistic effect of vinegar processing. Materials and methods Composition change rule after vinegar processing was applied by UPLC-QTOF-MS/MS coupled with principal component analysis (PCA). Based on our previous research, this paper expounded the action mechanism from the perspective of reducing biofilm toxicity and increasing antioxidant activity. Direct toxicity reducing information was obtained at the cellular level including cellular morphology, MTT assays, western blots and RT-PCR in L02 cells with overload sphingomyelin (SM). The synergistic effect was investigated through histological examinations, mesenteric hemorheology, ELISA, flow cytometry and confocal microscopy. Results It was found that the structure of PTS take place a series of chemical reactions in the process of vinegar processing which enabled the more toxic components transformed into less toxic components and components with clear efficacy, so as to achieve the purpose of detoxification and synergistic effect. The results indicated that the mechanism of detoxification in vinegar processing was that vinegar processing could act on SM, cause less balance disturbance to sphingomyelin/ceramide (SM/Cer), inhibit apoptosis and then alleviate toxicity. In addition, the pharmacodynamic results showed that the vinegar processing could have an obvious synergistic effect through anti-oxidant stress. Conclusions By changing the structures of the PTS, the SM/Cer disrupt was reduced and the antioxidant activity was enhanced, so as to decrease toxicity and increase efficiency in vinegar processing phytomedicines containing PTS.
研究领域:
民族药理学
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药理学
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中药学
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化学
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毒理学
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产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2025
·
IF 14.1
Hao Yan,Xiangliang Huang,Yourong Zhou,Yuan Mu,Shaoyin Zhang,Yashi Cao,Wentong Wu,Zhifei Xu,Xueqin Chen,Xiaochen Zhang,Xiaohong Wang,Xiaochun Yang,Bo Yang,Qiaojun He,Peihua Luo
Metabolic disorders have been identified as one of the causes of drug-induced liver injury; however, the direct regulatory mechanism regarding this disorder has not yet been clarified. In this study, a single regulatory mechanism of small molecule kinase inhibitors, with crizotinib as the representative drug is elucidated. First, it is discovered that crizotinib induced aberrant lipid metabolism and apoptosis in the liver. A mechanistic study revealed that crizotinib treatment promoted the accumulation of squalene epoxidase (SQLE) by inhibiting autophagosome-lysosome fusion which blocked the autophagic degradation of SQLE. A maladaptive increase in SQLE led to disturbances in cholesterol and sphingolipid metabolism via an enzymatic activity-dependent manner. Abnormal cholesterol results in both steatosis and inflammatory infiltration, and disturbances in sphingolipid metabolism promote cell apoptosis by inducing lysosomal membrane permeabilization. The restoration of the level or activity of SQLE ameliorated steatosis and hepatocyte injury. The autophagy activator known as metformin or the SQLE enzymatic inhibitor known as terbinafine has potential clinical use for alleviating crizotinib hepatotoxicity.
研究领域:
药理学
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肝病学
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分子生物学
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药物毒理学
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产品关联
DOI
PubMed
高影响因子
LANGMUIR
·
2024
·
IF 3.7
Xianhui Cheng,Yujuan Miao,Juntao Zhou,Feng Lu,Jingji Jin,Lianghai Hu
Plasma membranes not only maintain the intracellular microenvironment through their phospholipid bilayer but also eliminate exogenous compounds outside the cell membranes. Most drugs especially with high polarity are prevented from entering into cells to exert their effects. Therefore, it is of great significance to design effective drug carriers with a penetrating ability toward plasma membranes. In this study, a dual-templated MIP (dt-MIPs) carrier with controllable microstructure and high drug loading capacity was prepared using highly expressed sphingomyelin on the plasma membrane and tenofovir (TFV), a first-line drug for HIV and chronic hepatitis B, as template molecules. The drug release experiments performed in vitro under simulated physiological conditions demonstrated that sustained and stable adsorption of TFV on dt-MIPs was more than 80% over 50 h. By a combination of flow cytometry and confocal microscopy, dt-MIPs were found to have efficient cell permeability. Furthermore, mass-spectrometry-based intracellular pharmacokinetic studies demonstrated that TFV was delivered completely into cells within 30 min with the delivery of dt-MIPs. The study presented above suggested that dt-MIPs are expected to be alternative nanoscale drug carriers for enhanced drug permeability and controlled release.
研究领域:
药学
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纳米技术
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药物递送系统
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2025
·
IF 6.7
Jinlei Yang,Tianyi Liao,Pingping Zhang,Runsong Cheng,Jing Wang,Siyuan Pan,Murong Du,Boya Zhao,Weiliang Liu,Liying Yan,Sichun Zhang,Xinrong Zhang
Lipid regulation and remodeling are pivotal in follicle development and oocyte maturation. Performing lipidome analysis on single oocytes is essential for optimizing assisted reproductive techniques and improving pregnancy outcomes. Conventional organic solvent extraction faces challenges in single-cell analysis, including excessive sample dilution and time-consuming processing. In this study, we developed an on-valve microflow supercritical fluid extraction and chromatography–mass spectrometry (μSFE-SFC-MS) method. Lipids in intact single oocytes are extracted online by supercritical carbon dioxide fluid, separated by a C18 capillary column, ionized, and annotated. Notably, this method significantly reduces sample pretreatment and chromatographic separation time to just 15 min per sample, compared to about 2 h of the conventional method. We analyzed of 276 lipid species from a single oocyte. Lipidomic differences in oocyte maturation stages clarify distinct metabolic remodeling of phospholipids into sphingomyelins and glycerides. The differential analysis suggests that several lipid species can be used as criteria for determining oocyte maturation at the single-cell level. The present work offers a fast and high-coverage lipidomic analysis for single oocytes, also providing a workflow for other single-cell and trace samples.
研究领域:
分析化学
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脂质组学
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生殖生物学
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质谱分析
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色谱分析
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代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）