Acrylamide is classified as a Class 2A carcinogen and mainly metabolized to produce hepatotoxicity.Phosphatidylcholine is thought to protect the liver from damage,but the protective role of phosphatidylcholine on acry...Acrylamide is classified as a Class 2A carcinogen and mainly metabolized to produce hepatotoxicity.Phosphatidylcholine is thought to protect the liver from damage,but the protective role of phosphatidylcholine on acrylamide-exposed metabolic disorders remains unclear.We investigated protective effect of phosphatidylcholine on the hepatic metabolism in rats exposed to acrylamide using metabolomics and molecular biology approaches.Overall,32 endogenous effect biomarkers and 4 exposure biomarkers were identified as differential signature metabolites responsible for acrylamide exposure and phosphatidylcholine protection.Acrylamide exposure interferes with glutathione metabolism by consuming antioxidant glutathione,cysteine and L-ascorbic acid,and disrupts lipid and carbohydrate metabolism through reducing carnitine content and increasing lipid peroxidation.The phosphatidylcholine treatment reduces the expression of cytochrome P4502E1,alleviates the oxidative stress and inflammation of the liver,and stabilizes the content of glutathione,and thus alleviates the disorder of glutathione.Meanwhile,phosphatidylcholine shifted acrylamide-induced phosphatidylcholine into lysophosphatidylcholine to storage from lysophosphatidylcholine to diacylglycerol,thereby maintaining metabolic homeostasis of glycerophospholipid.The results suggested that phosphatidylcholine supplementation alleviate the disorder of glutathione and lipid metabolism caused by acrylamide exposure,but not significantly change the levels of mercapturic acid adducts of acrylamide,providing the evidence for phosphatidylcholine protection against acrylamide-induced liver injury.展开更多
Background:Diabetic kidney disease(DKD)is a major cause of end-stage renal disease,with limited effective treatment options currently available.Shenqi Dihuang Decoction(SQDH)has demonstrated clinical efficacy in manag...Background:Diabetic kidney disease(DKD)is a major cause of end-stage renal disease,with limited effective treatment options currently available.Shenqi Dihuang Decoction(SQDH)has demonstrated clinical efficacy in managing DKD;however,the metabolic mechanisms responsible for its therapeutic effects remain unclear.Methods:We established a DKD mouse model and treated the mice with SQDH to investigate its effects on renal function and tissue pathology.To explore the metabolic mechanisms,we conducted non-targeted metabolomics to identify differential metabolites in the renal tissues of DKD mice and the associated metabolic pathways affected by SQDH.Additionally,we performed RT-qPCR and Western blot analyses to assess the effects of SQDH on the expression of key genes and proteins within the targeted pathways.To further evaluate SQDH’s therapeutic effects,we measured oxidative stress markers and inflammatory factors,examining its antioxidant and anti-inflammatory properties in DKD.Results:SQDH treatment improved body weight and blood glucose levels in DKD mice.It also restored renal function,as indicated by improved 24h-UTP,serum creatinine,and blood urea nitrogen levels,and alleviated renal tissue pathology associated with DKD.Metabolomic analysis showed that SQDH primarily regulates glycerophospholipid metabolism,particularly by increasing phosphatidylcholine(PC)levels and decreasing lysophosphatidylcholine(LPC)levels.RT-qPCR and Western blot analyses revealed that SQDH upregulated LPCAT expression and downregulated PLA2G expression.Additionally,SQDH enhanced the activities of superoxide dismutase and glutathione peroxidase,reduced reactive oxygen species,4-hydroxy-2-nonenal,and malondialdehyde levels,and decreased the levels of inflammatory cytokines IL-1β,IL-6,and TNF-α.Conclusion:Our findings confirm that SQDH protects against DKD by regulating glycerophospholipid metabolism,restoring the balance of PC and LPC,inhibiting inflammatory responses,and reducing oxidative stress.展开更多
Objective To compare the serum glycerophospholipid levels in the inflammatory subtypes of asthma by using targeted metabolomic analysis. Methods Demographic and clinical data were collected from 51 patients with asthm...Objective To compare the serum glycerophospholipid levels in the inflammatory subtypes of asthma by using targeted metabolomic analysis. Methods Demographic and clinical data were collected from 51 patients with asthma between January 2015 and December 2015. Routine blood and sputum induction tests were performed. Eosinophilic asthma was defined as induced sputum containing ≥ 3% eosinophils, and neutrophilic asthma, as induced sputum containing ≥ 71% neutrophils. Serum metabolic glycerophospholipid profile was determined by liquid chromatography-mass spectrometry. Differences in glycerophospholipid levels between eosinophilic and non-eosinophilic asthma and between neutrophilic and non-neutrophilic asthma were analyzed using partial least squares discriminant analysis. Results The serum lysophosphatidylglycerol level was significantly higher in the group with ≥ 3% eosinophils in sputum than in the group with < 3% eosinophils in sputum. The area under the receiver-operating characteristic curve was ≥ 70%. There was no significant difference in the serum metabolic glycerophospholipid profile between the group with sputum neutrophils ≥ 71% and the group with sputum neutrophils < 71%. Conclusion Serum lysophosphatidylglycerol is produced abundantly in eosinophilic asthma and may be a biomarker of eosinophilic asthma. This information is helpful for identifying and tailoring treatment for the common asthma subtypes.展开更多
Verbascoside,abundant in olive mill wastewater,is a phenylethanolic glycoside with a wide range of pharmacological activities.Atherosclerosis(AS)is a common metabolic disease and abnormal lipid metabolism in liver is ...Verbascoside,abundant in olive mill wastewater,is a phenylethanolic glycoside with a wide range of pharmacological activities.Atherosclerosis(AS)is a common metabolic disease and abnormal lipid metabolism in liver is inseparable from its formation and development.In this study,the anti-atherosclerotic effect of verbascoside was evaluated by establishing an atherosclerosis model based on western diet feeding of apolipoprotein E-defi cient mice for 16 weeks.After 12 weeks of administration during the feeding period,the levels of total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C)in the plasma of mice were signifi cantly decreased,the formation of arterial plaques was delayed,and the levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST)and lactate dehydrogenase(LDH)in plasma were alleviated,showing the hepatoprotective effect.In addition,based on untargeted lipidomic analysis,verbascoside stabilized glycerophospholipid metabolism,modulated lipid metabolism disorders and reduced lipid deposition in the liver to achieve the therapeutic effi cacy against atherosclerosis by regulating cardiolipin(CL),ether-linked phosphatidylcholine(ether-PC),lysophophatidylcholine(LPC),phosphatidylcholine(PC),oxidized phosphatidylcholine(OxPC),oxidized phosphatidylethanolamine(OxPE),triacylglycerol(TG),sphingomyelin(SM)back to normal levels.展开更多
BACKGROUND Based on the breakthrough of genomics analysis, The Cancer Genome Atlas Research Group recently proposed an integrative genomic analysis, dividing gastric cancer(GC) into four subtypes, characterized by the...BACKGROUND Based on the breakthrough of genomics analysis, The Cancer Genome Atlas Research Group recently proposed an integrative genomic analysis, dividing gastric cancer(GC) into four subtypes, characterized by the chromosomal instability(CIN) status. However, the CIN status of GC is still vaguely characterized and lacking the valuable easy-to-use CIN markers to diagnosis in molecular and histological detection.AIM To explore the associations of CIN with downstream lipidomics profiles.METHODS We collected cancerous and noncancerous tissue samples from 18 patients with GC; the samples were divided into CIN and non-CIN types based on the system of The Cancer Genome Atlas Research Group and 409 sequenced oncogenes and tumor suppressor genes. We identified the lipidomics profiles of the GC samples and samples of their adjacent noncancerous tissues by using liquid chromatography–mass spectrometry. Furthermore, we selected leading metabolites based on variable importance in projection scores of > 1.0 and P <0.05.RESULTS Twelve men and six women participated in this study; the participants had a median age of 67.5 years(range, 52–87 years) and were divided into CIN(n = 9)and non-CIN(n = 9) groups. The GC samples exhibited distinct profiles of lysophosphocholine, phosphocholine, phosphatidylethanolamine,phosphatidylinositol, phosphoserine, sphingomyelin, ceramide, and triglycerides compared with their adjacent noncancerous tissues. The glycerophospholipid levels(phosphocholine, phosphatidylethanolamine, and phosphatidylinositol)were 1.4-to 2.3-times higher in the CIN group compared with the non-CIN group(P < 0.05). Alterations in the glycerolipid and glycerophospholipid pathways indicated progression of GC toward CIN.CONCLUSION The lipidomics profiles of GC samples were distinct from those of their adjacent noncancerous tissues. CIN status of GC is primarily associated with downstream lipidomics in the glycerophospholipid pathway.展开更多
OBJECTIVE Forsythiae Fructus(Lianqiao)is a typical heat-clearing and detoxicating traditional Chinese medicine(TCM)herb,which has been traditionally used for treating cancer according to TCM theory.However,the underly...OBJECTIVE Forsythiae Fructus(Lianqiao)is a typical heat-clearing and detoxicating traditional Chinese medicine(TCM)herb,which has been traditionally used for treating cancer according to TCM theory.However,the underlying mechanism has not been fully explained.METHODS In this study,we investigated the antitumor effect of Forsythiae Fructus aqueous extract(FAE)on B16-F10 melanoma.RESULTS FAE strongly inhibited the tumor growth and metastasis formation in B16-F10 melanoma transplanted mice.The survival time of tumor-bearing mice was also significantly prolonged by FAE.The levels of ROS,MDA,TNF-αand IL-6 decreased,while GSH increased in the FAE treatment group,indicating FAE possesses strong anti-oxidative and anti-inflammatory activity.Western blotting analysis demonstrated that antioxidant proteins Nrf2 and HO-1,tumor suppressors P53 and p-PTEN,and the MAPK pathways in tumor tissues were upregulated by FAE treatment.Serum metabolomics analysis further uncovered that 17 metabolites mostly involving in glycerophospholipid metabolism were correlated with the antitumor effect of FAE.Notably,several lysophosphatidylcholines(LysoPCs)significantly decreased in tumor model group,while FAE treatment restored the changes of these phospholipids to about normal condition.LysoPC acyltransferase 1(LPCAT1)and autotaxin(ATX)highly expressed in melanoma and markedly downregulated by FAE were believed to be responsible for this modulation.CONCLUSION FAE exhibites strong antitumor activity against B16-F10 melanoma through activating MAPKs/Nrf2/HO-1 mediated anti-oxidation and anti-inflammation and modulating glycerophospholipid metabolism via downregulating LPCAT1 and ATX.Besides,it is suggested that serum LysoPCs could be potential biomarkers for the diagnosis and prognosis of melanoma.展开更多
Phospholipids are the major building blocks of the biological membranes. Additionally, phospholipids modulate membrane trafficking and metabolites derived from their
Synapses are key structures involved in transmitting information in the nervous system,and their functions rely on the regulation of various lipids.Lipids play important roles in synapse formation,neurotransmitter rel...Synapses are key structures involved in transmitting information in the nervous system,and their functions rely on the regulation of various lipids.Lipids play important roles in synapse formation,neurotransmitter release,and signal transmission,and dysregulation of lipid metabolism is closely associated with various neurodegenerative diseases.The complex roles of lipids in synaptic function and neurological diseases have recently garnered increasing attention,but their specific mechanisms remain to be fully understood.This review aims to explore how lipids regulate synaptic activity in the central nervous system,focusing on their roles in synapse formation,neurotransmitter release,and signal transmission.Additionally,it discusses the mechanisms by which glial cells modulate synaptic function through lipid regulation.This review shows that within the central nervous system,lipids are essential components of the cell membrane bilayer,playing critical roles in synaptic structure and function.They regulate presynaptic vesicular trafficking,postsynaptic signaling pathways,and glial-neuronal interactions.Cholesterol maintains membrane fluidity and promotes the formation of lipid rafts.Glycerophospholipids contribute to the structural integrity of synaptic membranes and are involved in the release of synaptic vesicles.Sphingolipids interact with synaptic receptors through various mechanisms to regulate their activity and are also involved in cellular processes such as inflammation and apoptosis.Fatty acids are vital for energy metabolism and the synthesis of signaling molecules.Abnormalities in lipid metabolism may lead to impairments in synaptic function,affecting information transmission between neurons and the overall health of the nervous system.Therapeutic strategies targeting lipid metabolism,particularly through cholesterol modulation,show promise for treating these conditions.In neurodegenerative diseases such as Alzheimer’s disease,Parkinson disease,and amyotrophic lateral sclerosis,dysregulation of lipid metabolism is closely linked to synaptic dysfunction.Therefore,lipids are not only key molecules in neural regeneration and synaptic repair but may also contribute to neurodegenerative pathology when metabolic dysregulation occurs.Further research is needed to elucidate the specific mechanisms linking lipid metabolism to synaptic dysfunction and to develop targeted lipid therapies for neurological diseases.展开更多
Background:Non-alcoholic fatty liver disease(NAFLD)is a liver disorder characterized by the accumulation and degeneration of fat in the liver cells,a condition that may further deteriorate and lead to cirrhosis and li...Background:Non-alcoholic fatty liver disease(NAFLD)is a liver disorder characterized by the accumulation and degeneration of fat in the liver cells,a condition that may further deteriorate and lead to cirrhosis and liver cancer.Numerous studies showed that metabolic dysfunction can promote NAFLD development.Linggui Zhugan Decoction(LGZGD)has therapeutic effects on NAFLD.The mechanism of LGZGD still remains unclear.This study was to examine the impact of LGZGD on the metabolic processes involved in the development of NAFLD.Methods:A mice model of NAFLD was treated with LGZGD.The therapeutic potential of LGZGD was evaluated by assessing the activity of transaminases,lipids levels of blood,and pathological changes in the liver of the mice model of NAFLD.Additionally,this study also evaluated the influence of LGZGD on liver inflammation and oxidative stress.Results:The results of untargeted metabolomics analysis showed that LGZGD reduced the disordered lipid metabolism in NAFLD mice.LGZGD improved the oxidative stress and also reduced the levels of pro-inflammatory cytokines in the liver.Untargeted metabolomics analysis of liver samples revealed that LGZGD treatment improved metabolic disorders,including alanine,aspartate,glutamate,glycerophospholipid metabolism,and citrate cycle.Further RT-qPCR and Western blot results showed that LGZGD could regulate the expression of key enzymes in the metabolic pathway of the citrate cycle,including ATP-citrate lyase(ACLY),alanine-glyoxylate aminotransferase-2(AGXT2),phosphatidylethanolamine N-methyltransferase(PEMT),and succinate dehydrogenase(SDH).Conclusion:We found that LGZGD can treat NAFLD by reducing inflammatory responses,inhibiting oxidative stress,regulating alanine,aspartate,glutamate,and glycerophospholipid metabolism,and citrate cycle pathways.展开更多
OBJECTIVE:To investigate the mechanisms of the effect of Shenji Guben(SJGB)decoction(参吉固本方)on chronic obstructive pulmonary disease(COPD).METHODS:A murine model of COPD was established through lipopolysaccharide(...OBJECTIVE:To investigate the mechanisms of the effect of Shenji Guben(SJGB)decoction(参吉固本方)on chronic obstructive pulmonary disease(COPD).METHODS:A murine model of COPD was established through lipopolysaccharide(LPS)nasal drops and passive smoke exposure,followed by evaluation of SJGB decoction efficacy via lung function tests and histological analysis.Non-targeted liquid chromatography-mass spectrometry(LC-MS)-based metabolomics was used to explore the mechanisms of SJGB decoction in COPD.RESULTS:We found that the SJGB decoction effectively reduced inflammatory cell infiltration in the airways and lungs,and improved lung function in the COPD model mice.LC-MS-based metabolomics identified 86 biomarkers in COPD models.Compared to the model group,SJGB decoction significantly altered 34 metabolites.Prostaglandin E2 and DL-Citrulline were highlighted as two representative differential metabolites.MetaboAnalyst 5.0 highlighted glycerophospholipid and riboflavin metabolisms as key pathways affected by SJGB decoction.CONCLUSION:This study evaluated the protective effect of SJGB decoction against COPD and provided insights into its potential mechanisms in COPD treatment.展开更多
Cantharidin (CTD), a natural compound used to treat multiple tumors in the clinic setting, has been limited due to acute kidney injury (AKI). However, the major cause of AKI and its underlying mechanism remain to be e...Cantharidin (CTD), a natural compound used to treat multiple tumors in the clinic setting, has been limited due to acute kidney injury (AKI). However, the major cause of AKI and its underlying mechanism remain to be elucidated. Serum creatinine (SCr) and blood urea nitrogen (BUN) were detected through pathological evaluation after CTD (1.5 mg/kg) oral gavage in mice in 3 days. Kidney lipidomics based on ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to investigate lipids disorder after CTD exposure in mice. Then, spatial metabolomics based on matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) was used to detect the kidney spatial distribution of lipids. Integrative analysis was performed to reveal the spatial lipid disorder mechanism and verify key lipids in vitro. The results showed that the levels of SCr and BUN were increased, and tubular necrosis was observed in mouse kidneys, resulting in acute tubular necrosis (ATN) in CTD-induced AKI. Then, lipidomics results revealed that after CTD exposure, 232 differential lipid metabolites and 11 pathways including glycerophospholipid (GP) and sphingolipid (SL) metabolism were disrupted. Spatial metabolomics revealed that 55 spatial differential lipid metabolites and nine metabolic pathways were disturbed. Subsequently, integrative analysis found that GP metabolism was stimulated in the renal cortex and medulla, whereas SL metabolism was inhibited in the renal cortex. Up-regulated lysophosphatidylcholine (LysoPC) (18:2(9Z,12Z)), LysoPC (16:0/0:0), glycerophosphocholine, and down-regulated sphingomyelin (SM) (d18:0/16:0), SM (d18:1/24:0), and SM (d42:1) were key differential lipids. Among them, LysoPC (16:0/0:0) was increased in the CTD group at 1.1196 μg/mL, which aggravated CTD-induced ATN in human kidney-2 (HK-2) cells. LysoPC acyltransferase was inhibited and choline phosphotransferase 1 (CEPT1) was activated after CTD intervention in mice and in HK-2 cells. CTD induces ATN, resulting in AKI, by activating GP metabolism and inhibiting SL metabolism in the renal cortex and medulla, LysoPC (16:0/0:0), LysoPC acyltransferase, and CEPT1 may be the therapeutic targets.展开更多
基金supported by the National Natural Science Foundation of China(21976156)。
文摘Acrylamide is classified as a Class 2A carcinogen and mainly metabolized to produce hepatotoxicity.Phosphatidylcholine is thought to protect the liver from damage,but the protective role of phosphatidylcholine on acrylamide-exposed metabolic disorders remains unclear.We investigated protective effect of phosphatidylcholine on the hepatic metabolism in rats exposed to acrylamide using metabolomics and molecular biology approaches.Overall,32 endogenous effect biomarkers and 4 exposure biomarkers were identified as differential signature metabolites responsible for acrylamide exposure and phosphatidylcholine protection.Acrylamide exposure interferes with glutathione metabolism by consuming antioxidant glutathione,cysteine and L-ascorbic acid,and disrupts lipid and carbohydrate metabolism through reducing carnitine content and increasing lipid peroxidation.The phosphatidylcholine treatment reduces the expression of cytochrome P4502E1,alleviates the oxidative stress and inflammation of the liver,and stabilizes the content of glutathione,and thus alleviates the disorder of glutathione.Meanwhile,phosphatidylcholine shifted acrylamide-induced phosphatidylcholine into lysophosphatidylcholine to storage from lysophosphatidylcholine to diacylglycerol,thereby maintaining metabolic homeostasis of glycerophospholipid.The results suggested that phosphatidylcholine supplementation alleviate the disorder of glutathione and lipid metabolism caused by acrylamide exposure,but not significantly change the levels of mercapturic acid adducts of acrylamide,providing the evidence for phosphatidylcholine protection against acrylamide-induced liver injury.
基金supported by the Hebei Provincial Administration of Traditional Chinese Medicine 2022 Chinese medicine research program mandatory subject(2021.No.12)Hebei famous traditional Chinese medicine inheritance studio construction project(2024.No.37)Yunnan Fundamental Research Projects(grant No.202501AT070266).
文摘Background:Diabetic kidney disease(DKD)is a major cause of end-stage renal disease,with limited effective treatment options currently available.Shenqi Dihuang Decoction(SQDH)has demonstrated clinical efficacy in managing DKD;however,the metabolic mechanisms responsible for its therapeutic effects remain unclear.Methods:We established a DKD mouse model and treated the mice with SQDH to investigate its effects on renal function and tissue pathology.To explore the metabolic mechanisms,we conducted non-targeted metabolomics to identify differential metabolites in the renal tissues of DKD mice and the associated metabolic pathways affected by SQDH.Additionally,we performed RT-qPCR and Western blot analyses to assess the effects of SQDH on the expression of key genes and proteins within the targeted pathways.To further evaluate SQDH’s therapeutic effects,we measured oxidative stress markers and inflammatory factors,examining its antioxidant and anti-inflammatory properties in DKD.Results:SQDH treatment improved body weight and blood glucose levels in DKD mice.It also restored renal function,as indicated by improved 24h-UTP,serum creatinine,and blood urea nitrogen levels,and alleviated renal tissue pathology associated with DKD.Metabolomic analysis showed that SQDH primarily regulates glycerophospholipid metabolism,particularly by increasing phosphatidylcholine(PC)levels and decreasing lysophosphatidylcholine(LPC)levels.RT-qPCR and Western blot analyses revealed that SQDH upregulated LPCAT expression and downregulated PLA2G expression.Additionally,SQDH enhanced the activities of superoxide dismutase and glutathione peroxidase,reduced reactive oxygen species,4-hydroxy-2-nonenal,and malondialdehyde levels,and decreased the levels of inflammatory cytokines IL-1β,IL-6,and TNF-α.Conclusion:Our findings confirm that SQDH protects against DKD by regulating glycerophospholipid metabolism,restoring the balance of PC and LPC,inhibiting inflammatory responses,and reducing oxidative stress.
基金funded by the National Natural Science Foundation of China Youth Fund Project [No.81400017]the National Natural Science Foundation of China Emergency Management Project [No.81641153]the Returned Overseas Chinese Scholars Startup Fund [No.Y81484-02]
文摘Objective To compare the serum glycerophospholipid levels in the inflammatory subtypes of asthma by using targeted metabolomic analysis. Methods Demographic and clinical data were collected from 51 patients with asthma between January 2015 and December 2015. Routine blood and sputum induction tests were performed. Eosinophilic asthma was defined as induced sputum containing ≥ 3% eosinophils, and neutrophilic asthma, as induced sputum containing ≥ 71% neutrophils. Serum metabolic glycerophospholipid profile was determined by liquid chromatography-mass spectrometry. Differences in glycerophospholipid levels between eosinophilic and non-eosinophilic asthma and between neutrophilic and non-neutrophilic asthma were analyzed using partial least squares discriminant analysis. Results The serum lysophosphatidylglycerol level was significantly higher in the group with ≥ 3% eosinophils in sputum than in the group with < 3% eosinophils in sputum. The area under the receiver-operating characteristic curve was ≥ 70%. There was no significant difference in the serum metabolic glycerophospholipid profile between the group with sputum neutrophils ≥ 71% and the group with sputum neutrophils < 71%. Conclusion Serum lysophosphatidylglycerol is produced abundantly in eosinophilic asthma and may be a biomarker of eosinophilic asthma. This information is helpful for identifying and tailoring treatment for the common asthma subtypes.
基金supported by the Tianjin Science and Technology Project(21ZYJDJC00080)and(20ZYJDJC00120)the Natural Science Foundation of Tianjin(18JCZDJC97700)the Natural Science Foundation of China(81573547).
文摘Verbascoside,abundant in olive mill wastewater,is a phenylethanolic glycoside with a wide range of pharmacological activities.Atherosclerosis(AS)is a common metabolic disease and abnormal lipid metabolism in liver is inseparable from its formation and development.In this study,the anti-atherosclerotic effect of verbascoside was evaluated by establishing an atherosclerosis model based on western diet feeding of apolipoprotein E-defi cient mice for 16 weeks.After 12 weeks of administration during the feeding period,the levels of total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C)in the plasma of mice were signifi cantly decreased,the formation of arterial plaques was delayed,and the levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST)and lactate dehydrogenase(LDH)in plasma were alleviated,showing the hepatoprotective effect.In addition,based on untargeted lipidomic analysis,verbascoside stabilized glycerophospholipid metabolism,modulated lipid metabolism disorders and reduced lipid deposition in the liver to achieve the therapeutic effi cacy against atherosclerosis by regulating cardiolipin(CL),ether-linked phosphatidylcholine(ether-PC),lysophophatidylcholine(LPC),phosphatidylcholine(PC),oxidized phosphatidylcholine(OxPC),oxidized phosphatidylethanolamine(OxPE),triacylglycerol(TG),sphingomyelin(SM)back to normal levels.
基金the funding from the Ministry of Science and Technology Taiwan grant,No.MOST 106-2314-B-182A-019-MY3the Chang Gung Foundation,No.CMRPG3E1321-2
文摘BACKGROUND Based on the breakthrough of genomics analysis, The Cancer Genome Atlas Research Group recently proposed an integrative genomic analysis, dividing gastric cancer(GC) into four subtypes, characterized by the chromosomal instability(CIN) status. However, the CIN status of GC is still vaguely characterized and lacking the valuable easy-to-use CIN markers to diagnosis in molecular and histological detection.AIM To explore the associations of CIN with downstream lipidomics profiles.METHODS We collected cancerous and noncancerous tissue samples from 18 patients with GC; the samples were divided into CIN and non-CIN types based on the system of The Cancer Genome Atlas Research Group and 409 sequenced oncogenes and tumor suppressor genes. We identified the lipidomics profiles of the GC samples and samples of their adjacent noncancerous tissues by using liquid chromatography–mass spectrometry. Furthermore, we selected leading metabolites based on variable importance in projection scores of > 1.0 and P <0.05.RESULTS Twelve men and six women participated in this study; the participants had a median age of 67.5 years(range, 52–87 years) and were divided into CIN(n = 9)and non-CIN(n = 9) groups. The GC samples exhibited distinct profiles of lysophosphocholine, phosphocholine, phosphatidylethanolamine,phosphatidylinositol, phosphoserine, sphingomyelin, ceramide, and triglycerides compared with their adjacent noncancerous tissues. The glycerophospholipid levels(phosphocholine, phosphatidylethanolamine, and phosphatidylinositol)were 1.4-to 2.3-times higher in the CIN group compared with the non-CIN group(P < 0.05). Alterations in the glycerolipid and glycerophospholipid pathways indicated progression of GC toward CIN.CONCLUSION The lipidomics profiles of GC samples were distinct from those of their adjacent noncancerous tissues. CIN status of GC is primarily associated with downstream lipidomics in the glycerophospholipid pathway.
文摘OBJECTIVE Forsythiae Fructus(Lianqiao)is a typical heat-clearing and detoxicating traditional Chinese medicine(TCM)herb,which has been traditionally used for treating cancer according to TCM theory.However,the underlying mechanism has not been fully explained.METHODS In this study,we investigated the antitumor effect of Forsythiae Fructus aqueous extract(FAE)on B16-F10 melanoma.RESULTS FAE strongly inhibited the tumor growth and metastasis formation in B16-F10 melanoma transplanted mice.The survival time of tumor-bearing mice was also significantly prolonged by FAE.The levels of ROS,MDA,TNF-αand IL-6 decreased,while GSH increased in the FAE treatment group,indicating FAE possesses strong anti-oxidative and anti-inflammatory activity.Western blotting analysis demonstrated that antioxidant proteins Nrf2 and HO-1,tumor suppressors P53 and p-PTEN,and the MAPK pathways in tumor tissues were upregulated by FAE treatment.Serum metabolomics analysis further uncovered that 17 metabolites mostly involving in glycerophospholipid metabolism were correlated with the antitumor effect of FAE.Notably,several lysophosphatidylcholines(LysoPCs)significantly decreased in tumor model group,while FAE treatment restored the changes of these phospholipids to about normal condition.LysoPC acyltransferase 1(LPCAT1)and autotaxin(ATX)highly expressed in melanoma and markedly downregulated by FAE were believed to be responsible for this modulation.CONCLUSION FAE exhibites strong antitumor activity against B16-F10 melanoma through activating MAPKs/Nrf2/HO-1 mediated anti-oxidation and anti-inflammation and modulating glycerophospholipid metabolism via downregulating LPCAT1 and ATX.Besides,it is suggested that serum LysoPCs could be potential biomarkers for the diagnosis and prognosis of melanoma.
文摘Phospholipids are the major building blocks of the biological membranes. Additionally, phospholipids modulate membrane trafficking and metabolites derived from their
基金supported by the National Natural Science Foundation of China,No.82201568(to QQ)Capital’s Funds for Health Improvement and Research,No.2024-2-1031(to QQ)Beijing Nova Program,No.20240484566(to QQ).
文摘Synapses are key structures involved in transmitting information in the nervous system,and their functions rely on the regulation of various lipids.Lipids play important roles in synapse formation,neurotransmitter release,and signal transmission,and dysregulation of lipid metabolism is closely associated with various neurodegenerative diseases.The complex roles of lipids in synaptic function and neurological diseases have recently garnered increasing attention,but their specific mechanisms remain to be fully understood.This review aims to explore how lipids regulate synaptic activity in the central nervous system,focusing on their roles in synapse formation,neurotransmitter release,and signal transmission.Additionally,it discusses the mechanisms by which glial cells modulate synaptic function through lipid regulation.This review shows that within the central nervous system,lipids are essential components of the cell membrane bilayer,playing critical roles in synaptic structure and function.They regulate presynaptic vesicular trafficking,postsynaptic signaling pathways,and glial-neuronal interactions.Cholesterol maintains membrane fluidity and promotes the formation of lipid rafts.Glycerophospholipids contribute to the structural integrity of synaptic membranes and are involved in the release of synaptic vesicles.Sphingolipids interact with synaptic receptors through various mechanisms to regulate their activity and are also involved in cellular processes such as inflammation and apoptosis.Fatty acids are vital for energy metabolism and the synthesis of signaling molecules.Abnormalities in lipid metabolism may lead to impairments in synaptic function,affecting information transmission between neurons and the overall health of the nervous system.Therapeutic strategies targeting lipid metabolism,particularly through cholesterol modulation,show promise for treating these conditions.In neurodegenerative diseases such as Alzheimer’s disease,Parkinson disease,and amyotrophic lateral sclerosis,dysregulation of lipid metabolism is closely linked to synaptic dysfunction.Therefore,lipids are not only key molecules in neural regeneration and synaptic repair but may also contribute to neurodegenerative pathology when metabolic dysregulation occurs.Further research is needed to elucidate the specific mechanisms linking lipid metabolism to synaptic dysfunction and to develop targeted lipid therapies for neurological diseases.
基金supported by the National Natural Science Foundation of China(82274424).
文摘Background:Non-alcoholic fatty liver disease(NAFLD)is a liver disorder characterized by the accumulation and degeneration of fat in the liver cells,a condition that may further deteriorate and lead to cirrhosis and liver cancer.Numerous studies showed that metabolic dysfunction can promote NAFLD development.Linggui Zhugan Decoction(LGZGD)has therapeutic effects on NAFLD.The mechanism of LGZGD still remains unclear.This study was to examine the impact of LGZGD on the metabolic processes involved in the development of NAFLD.Methods:A mice model of NAFLD was treated with LGZGD.The therapeutic potential of LGZGD was evaluated by assessing the activity of transaminases,lipids levels of blood,and pathological changes in the liver of the mice model of NAFLD.Additionally,this study also evaluated the influence of LGZGD on liver inflammation and oxidative stress.Results:The results of untargeted metabolomics analysis showed that LGZGD reduced the disordered lipid metabolism in NAFLD mice.LGZGD improved the oxidative stress and also reduced the levels of pro-inflammatory cytokines in the liver.Untargeted metabolomics analysis of liver samples revealed that LGZGD treatment improved metabolic disorders,including alanine,aspartate,glutamate,glycerophospholipid metabolism,and citrate cycle.Further RT-qPCR and Western blot results showed that LGZGD could regulate the expression of key enzymes in the metabolic pathway of the citrate cycle,including ATP-citrate lyase(ACLY),alanine-glyoxylate aminotransferase-2(AGXT2),phosphatidylethanolamine N-methyltransferase(PEMT),and succinate dehydrogenase(SDH).Conclusion:We found that LGZGD can treat NAFLD by reducing inflammatory responses,inhibiting oxidative stress,regulating alanine,aspartate,glutamate,and glycerophospholipid metabolism,and citrate cycle pathways.
基金Supported by Traditional Chinese Medicine Science and Technology Development Plan of Jiangsu Province (No. MS2021013, ZD202215):Exploring the Efficacy and Mechanism of Professor Cao Shihong's Shenji Guben Decoction in Treating Chronic Obstructive Pulmonary Disease Based on Metabolomicsa Real-World Cohort Study on Traditional Chinese Medicine for the Treatment of Acute Exacerbation of Chronic Obstructive Pulmonary DiseaseIntra-hospital Fund of Jiangsu Provincial Hospital of Traditional Chinese Medicine Development (No. Y2021ZR11):Investigating the Mechanism of Shenji Guben Decoction in Treating Chronic Obstructive Pulmonary Disease Based on Metabolomics
文摘OBJECTIVE:To investigate the mechanisms of the effect of Shenji Guben(SJGB)decoction(参吉固本方)on chronic obstructive pulmonary disease(COPD).METHODS:A murine model of COPD was established through lipopolysaccharide(LPS)nasal drops and passive smoke exposure,followed by evaluation of SJGB decoction efficacy via lung function tests and histological analysis.Non-targeted liquid chromatography-mass spectrometry(LC-MS)-based metabolomics was used to explore the mechanisms of SJGB decoction in COPD.RESULTS:We found that the SJGB decoction effectively reduced inflammatory cell infiltration in the airways and lungs,and improved lung function in the COPD model mice.LC-MS-based metabolomics identified 86 biomarkers in COPD models.Compared to the model group,SJGB decoction significantly altered 34 metabolites.Prostaglandin E2 and DL-Citrulline were highlighted as two representative differential metabolites.MetaboAnalyst 5.0 highlighted glycerophospholipid and riboflavin metabolisms as key pathways affected by SJGB decoction.CONCLUSION:This study evaluated the protective effect of SJGB decoction against COPD and provided insights into its potential mechanisms in COPD treatment.
基金supported by the National Natural Science Foundation of China(Grant Nos.:82260812 and 81803838)the Guizhou Provincial Science&Technology Program,China(Project Nos.:YQK[2023]038 and[2020]5007)+1 种基金the Beijing Natural Science Foundation,China(Grant No.:7254489)the Science and Technology Program of Zunyi city of Guizhou province of China(Project Nos.:(2022)420,[2021]-3,[2020]7,and(2022)419).
文摘Cantharidin (CTD), a natural compound used to treat multiple tumors in the clinic setting, has been limited due to acute kidney injury (AKI). However, the major cause of AKI and its underlying mechanism remain to be elucidated. Serum creatinine (SCr) and blood urea nitrogen (BUN) were detected through pathological evaluation after CTD (1.5 mg/kg) oral gavage in mice in 3 days. Kidney lipidomics based on ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to investigate lipids disorder after CTD exposure in mice. Then, spatial metabolomics based on matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) was used to detect the kidney spatial distribution of lipids. Integrative analysis was performed to reveal the spatial lipid disorder mechanism and verify key lipids in vitro. The results showed that the levels of SCr and BUN were increased, and tubular necrosis was observed in mouse kidneys, resulting in acute tubular necrosis (ATN) in CTD-induced AKI. Then, lipidomics results revealed that after CTD exposure, 232 differential lipid metabolites and 11 pathways including glycerophospholipid (GP) and sphingolipid (SL) metabolism were disrupted. Spatial metabolomics revealed that 55 spatial differential lipid metabolites and nine metabolic pathways were disturbed. Subsequently, integrative analysis found that GP metabolism was stimulated in the renal cortex and medulla, whereas SL metabolism was inhibited in the renal cortex. Up-regulated lysophosphatidylcholine (LysoPC) (18:2(9Z,12Z)), LysoPC (16:0/0:0), glycerophosphocholine, and down-regulated sphingomyelin (SM) (d18:0/16:0), SM (d18:1/24:0), and SM (d42:1) were key differential lipids. Among them, LysoPC (16:0/0:0) was increased in the CTD group at 1.1196 μg/mL, which aggravated CTD-induced ATN in human kidney-2 (HK-2) cells. LysoPC acyltransferase was inhibited and choline phosphotransferase 1 (CEPT1) was activated after CTD intervention in mice and in HK-2 cells. CTD induces ATN, resulting in AKI, by activating GP metabolism and inhibiting SL metabolism in the renal cortex and medulla, LysoPC (16:0/0:0), LysoPC acyltransferase, and CEPT1 may be the therapeutic targets.
