Chagas disease (CD) affects 21 countries in the Americas and is caused by the parasite Trypanosoma cruzi. A key molecule involved in CD is lysophosphatidylcholine (LPC), which has been studied in various contexts: in ...Chagas disease (CD) affects 21 countries in the Americas and is caused by the parasite Trypanosoma cruzi. A key molecule involved in CD is lysophosphatidylcholine (LPC), which has been studied in various contexts: in the saliva of insect vectors, during the establishment of infection in the vertebrate host, and for the parasite itself. This lipid can be produced by the action of phospholipases A2 (PLA2), enzymes that catalyze the hydrolysis of phospholipids releasing fatty acids and lysophospholipids, such as LPC. This study investigates LPC levels and PLA2 activities in the plasma of CD patients and compares these levels with those in healthy individuals and patients with idiopathic dilated cardiomyopathy (IDCM). Plasma from 64 CD patients, 54 healthy individuals, and 16 IDCM patients were analyzed. LPC levels and the activity of two types of phospholipase A2: secreted (sPLA2) and lipoprotein-associated (Lp-PLA2) were measured. LPC levels and sPLA2 activity were similar between CD patients and the control groups. However, there were notable differences in LPC levels and sPLA2 activity between subgroups of CD patients and IDCM patients. This study is the first to identify LPC in patients with CD across various stages of the disease. It also offers new insights into the biochemical changes observed in the plasma of patients with IDCM.展开更多
The stimulatory effect of lysophosphatidylcholine (lyso_PC) on ATP and ρ_nitrophenyl phosphate (PNPP) hydrolysis by the plasma membrane H +_ATPase from soybean (Glycine max (L.) Merr.) hypocotyls was studied. Re...The stimulatory effect of lysophosphatidylcholine (lyso_PC) on ATP and ρ_nitrophenyl phosphate (PNPP) hydrolysis by the plasma membrane H +_ATPase from soybean (Glycine max (L.) Merr.) hypocotyls was studied. Results showed that lyso_PC stimulated the hydrolysis of ATP; ATP hydrolysis was enhanced dramatically when lyso_PC was within 0-0.03%, and increased slightly when lyso_PC was higher than 0.03%. At the concentration of 0.03%, lyso_PC stimulated ATP hydrolysis by 80.5%. Kinetics analysis showed that V max increased from 0.46 μmol P i·mg -1 protein·min -1 to 0.87 μmol P i·mg -1 protein·min -1 while K m increased from 0.88 mmol/L to 1.15 mmol/L under lyso_PC treatment. The optimum pH of ATP hydrolysis was shifted from 6.5 to 7.0 . Moreover, it was found lyso_PC enhanced the inhibition of ATP hydrolysis by hydroxylamine. In the presence of 200 mmol/L hydroxylamine, ATP hydrolysis was inhibited by 74.4%, while it was inhibited by 84.4% when treated with lyso_PC. However, PNPP hydrolysis and the inhibitory effect of vanadate were not affected by lyso_PC. The above results indicated that the kinase domain might be an action site or regulatory region of the C_terminal autoinhibitory domain in the plant plasma membrane H +_ATPase.展开更多
Schwann cells play a major role in helping heal injured nerves. They help clear debris, produce neurotrophins, upregulate neurotrophin receptors, and form bands of Büngner to guide the healing nerve. But nerves d...Schwann cells play a major role in helping heal injured nerves. They help clear debris, produce neurotrophins, upregulate neurotrophin receptors, and form bands of Büngner to guide the healing nerve. But nerves do not always produce enough neurotrophins and neurotrophin receptors to repair themselves. Nerve growth factor（NGF） is an important neurotrophin for promoting nerve healing and lysophosphatidylcholine（LPC） has been shown to stimulate NGF receptors（NGFR）. This study tested the administration of a single intraneural injection of LPC（1 mg/mL for single LPC injection and 10 mg/mL for multiple LPC injections） at day 0 and one（day 7）, two（days 5 and 7）, or three（days 5, 7, and 9） injections of NGF（160 ng/mL for single injections and 80 ng/mL for multiple injections） to determine baseline effects on crush ed sciatic nerves in rats. The rats were randomly divided into four groups： control, crush, crush-NGF, and crush-LPC-NGF. The healing of the nerves was measured weekly by monitoring gait; electrophysiological parameters： compound muscle action potential（CMAP） amplitudes; and morphological parameters： total fascicle areas, myelinated fiber counts, fiber densities, fiber packing, and mean g-ratio values at weeks 3 and 6. The crush, crush-NGF, and crush-LPC-NGF groups statistically differed from the control group for all six weeks for the electrophysiological parameters but only differed from the control group at week 3 for the morphological parameters. The crush, crush-NGF, and crush-LPC-NGF groups did not differ from each other over the course of the study. Single injections of LPC and NGF one week apart or multiple treatments of NGF at 5, 7 and 9 days post-injury did not alter the healing rate of the sciatic nerves during weeks 1-6 of the study. These findings are important to define the baseline effects of NGF and LPC injections, as part of a larger effort to determine the minimal dose regimen of NGF to regenerate peripheral nerves.展开更多
AIM:To analyze phospholipid profiles in intrahepatic bile from patients with primary sclerosing cholangitis(PSC)and secondary sclerosing cholangitis(SSC).METHODS:Intrahepatic bile specimens collected via endoscopic re...AIM:To analyze phospholipid profiles in intrahepatic bile from patients with primary sclerosing cholangitis(PSC)and secondary sclerosing cholangitis(SSC).METHODS:Intrahepatic bile specimens collected via endoscopic retrograde cholangiography from 41 patients were analyzed.Fourteen of these patients were diagnosed with PSC,10 with SSC,11 with choledocholithiasis or no identifiable biliary disease,and 6 with cholangiocellular carcinoma(CCC).Bile acid,cholesterol,protein,and bilirubin contents as well as pancreas lipase activity in bile were determined by biochemical methods.Phosphatidylcholine(PC)and lysophosphatidylcholine(LPC)species were quantified using nanoelectrospray ionization tandem mass spectrometry.RESULTS:Bile from all the examined patient groups showed a remarkably similar PC and LPC species composition,with only minor statistical differences.Total biliary PC concentrations were highest in controls(8030±1843 mol/L)and lowest in patients with CCC(1969±981 mol/L)(P=0.005,controls vs SSC and CCC,respectively,P<0.05).LPC contents in bile were overall low(4.2%±1.8%).Biliary LPC/PC ratios and ratios of biliary PC to bilirubin,PC to cholesterol,PC to protein,and PC to bile acids showed no intergroup differences.CONCLUSION:PC and LPC profiles being similar in patients with or without sclerosing cholangitis,these phospholipids are likely not of major pathogenetic importance in this disease group.展开更多
The functional and structural integrity of the blood-brain barrier is crucial in maintaining homeostasis in the brain microenvironment;however,the molecular mechanisms underlying the formation and function of the bloo...The functional and structural integrity of the blood-brain barrier is crucial in maintaining homeostasis in the brain microenvironment;however,the molecular mechanisms underlying the formation and function of the blood-brain barrier remain poorly understood.The major facilitator superfamily domain containing 2A has been identified as a key regulator of blood-brain barrier function.It plays a critical role in promoting and maintaining the formation and functional stability of the blood-brain barrier,in addition to the transport of lipids,such as docosahexaenoic acid,across the blood-brain barrier.Furthermore,an increasing number of studies have suggested that major facilitator superfamily domain containing 2A is involved in the molecular mechanisms of blood-brain barrier dysfunction in a variety of neurological diseases;however,little is known regarding the mechanisms by which major facilitator superfamily domain containing 2A affects the blood-brain barrier.This paper provides a comprehensive and systematic review of the close relationship between major facilitator superfamily domain containing 2A proteins and the blood-brain barrier,including their basic structures and functions,cross-linking between major facilitator superfamily domain containing 2A and the blood-brain barrier,and the in-depth studies on lipid transport and the regulation of blood-brain barrier permeability.This comprehensive systematic review contributes to an in-depth understanding of the important role of major facilitator superfamily domain containing 2A proteins in maintaining the structure and function of the blood-brain barrier and the research progress to date.This will not only help to elucidate the pathogenesis of neurological diseases,improve the accuracy of laboratory diagnosis,and optimize clinical treatment strategies,but it may also play an important role in prognostic monitoring.In addition,the effects of major facilitator superfamily domain containing 2A on blood-brain barrier leakage in various diseases and the research progress on cross-blood-brain barrier drug delivery are summarized.This review may contribute to the development of new approaches for the treatment of neurological diseases.展开更多
文摘Chagas disease (CD) affects 21 countries in the Americas and is caused by the parasite Trypanosoma cruzi. A key molecule involved in CD is lysophosphatidylcholine (LPC), which has been studied in various contexts: in the saliva of insect vectors, during the establishment of infection in the vertebrate host, and for the parasite itself. This lipid can be produced by the action of phospholipases A2 (PLA2), enzymes that catalyze the hydrolysis of phospholipids releasing fatty acids and lysophospholipids, such as LPC. This study investigates LPC levels and PLA2 activities in the plasma of CD patients and compares these levels with those in healthy individuals and patients with idiopathic dilated cardiomyopathy (IDCM). Plasma from 64 CD patients, 54 healthy individuals, and 16 IDCM patients were analyzed. LPC levels and the activity of two types of phospholipase A2: secreted (sPLA2) and lipoprotein-associated (Lp-PLA2) were measured. LPC levels and sPLA2 activity were similar between CD patients and the control groups. However, there were notable differences in LPC levels and sPLA2 activity between subgroups of CD patients and IDCM patients. This study is the first to identify LPC in patients with CD across various stages of the disease. It also offers new insights into the biochemical changes observed in the plasma of patients with IDCM.
文摘The stimulatory effect of lysophosphatidylcholine (lyso_PC) on ATP and ρ_nitrophenyl phosphate (PNPP) hydrolysis by the plasma membrane H +_ATPase from soybean (Glycine max (L.) Merr.) hypocotyls was studied. Results showed that lyso_PC stimulated the hydrolysis of ATP; ATP hydrolysis was enhanced dramatically when lyso_PC was within 0-0.03%, and increased slightly when lyso_PC was higher than 0.03%. At the concentration of 0.03%, lyso_PC stimulated ATP hydrolysis by 80.5%. Kinetics analysis showed that V max increased from 0.46 μmol P i·mg -1 protein·min -1 to 0.87 μmol P i·mg -1 protein·min -1 while K m increased from 0.88 mmol/L to 1.15 mmol/L under lyso_PC treatment. The optimum pH of ATP hydrolysis was shifted from 6.5 to 7.0 . Moreover, it was found lyso_PC enhanced the inhibition of ATP hydrolysis by hydroxylamine. In the presence of 200 mmol/L hydroxylamine, ATP hydrolysis was inhibited by 74.4%, while it was inhibited by 84.4% when treated with lyso_PC. However, PNPP hydrolysis and the inhibitory effect of vanadate were not affected by lyso_PC. The above results indicated that the kinase domain might be an action site or regulatory region of the C_terminal autoinhibitory domain in the plant plasma membrane H +_ATPase.
基金Funding for animal care and supplies was provided by Brigham Young University,the Don B.Olsen Mentorship to RLWa Brigham Young University Office of Research and Creative Activities Student Mentored Research Grant to KSK
文摘Schwann cells play a major role in helping heal injured nerves. They help clear debris, produce neurotrophins, upregulate neurotrophin receptors, and form bands of Büngner to guide the healing nerve. But nerves do not always produce enough neurotrophins and neurotrophin receptors to repair themselves. Nerve growth factor（NGF） is an important neurotrophin for promoting nerve healing and lysophosphatidylcholine（LPC） has been shown to stimulate NGF receptors（NGFR）. This study tested the administration of a single intraneural injection of LPC（1 mg/mL for single LPC injection and 10 mg/mL for multiple LPC injections） at day 0 and one（day 7）, two（days 5 and 7）, or three（days 5, 7, and 9） injections of NGF（160 ng/mL for single injections and 80 ng/mL for multiple injections） to determine baseline effects on crush ed sciatic nerves in rats. The rats were randomly divided into four groups： control, crush, crush-NGF, and crush-LPC-NGF. The healing of the nerves was measured weekly by monitoring gait; electrophysiological parameters： compound muscle action potential（CMAP） amplitudes; and morphological parameters： total fascicle areas, myelinated fiber counts, fiber densities, fiber packing, and mean g-ratio values at weeks 3 and 6. The crush, crush-NGF, and crush-LPC-NGF groups statistically differed from the control group for all six weeks for the electrophysiological parameters but only differed from the control group at week 3 for the morphological parameters. The crush, crush-NGF, and crush-LPC-NGF groups did not differ from each other over the course of the study. Single injections of LPC and NGF one week apart or multiple treatments of NGF at 5, 7 and 9 days post-injury did not alter the healing rate of the sciatic nerves during weeks 1-6 of the study. These findings are important to define the baseline effects of NGF and LPC injections, as part of a larger effort to determine the minimal dose regimen of NGF to regenerate peripheral nerves.
基金Supported by A Grant from Deutsche Forschungsgemeinschaft(DFG)
文摘AIM:To analyze phospholipid profiles in intrahepatic bile from patients with primary sclerosing cholangitis(PSC)and secondary sclerosing cholangitis(SSC).METHODS:Intrahepatic bile specimens collected via endoscopic retrograde cholangiography from 41 patients were analyzed.Fourteen of these patients were diagnosed with PSC,10 with SSC,11 with choledocholithiasis or no identifiable biliary disease,and 6 with cholangiocellular carcinoma(CCC).Bile acid,cholesterol,protein,and bilirubin contents as well as pancreas lipase activity in bile were determined by biochemical methods.Phosphatidylcholine(PC)and lysophosphatidylcholine(LPC)species were quantified using nanoelectrospray ionization tandem mass spectrometry.RESULTS:Bile from all the examined patient groups showed a remarkably similar PC and LPC species composition,with only minor statistical differences.Total biliary PC concentrations were highest in controls(8030±1843 mol/L)and lowest in patients with CCC(1969±981 mol/L)(P=0.005,controls vs SSC and CCC,respectively,P<0.05).LPC contents in bile were overall low(4.2%±1.8%).Biliary LPC/PC ratios and ratios of biliary PC to bilirubin,PC to cholesterol,PC to protein,and PC to bile acids showed no intergroup differences.CONCLUSION:PC and LPC profiles being similar in patients with or without sclerosing cholangitis,these phospholipids are likely not of major pathogenetic importance in this disease group.
基金supported by the National Natural Science Foundation of China,No.82104412(to TD)Shaanxi Provincial Key R&D Program,No.2023-YBSF-165(to TD)+1 种基金the Natural Science Foundation of Shaanxi Department of Science and Technology,No.2018JM7022(to FM)Shaanxi Provincial Key Industry Chain Project,No.2021ZDLSF04-11(to PW)。
文摘The functional and structural integrity of the blood-brain barrier is crucial in maintaining homeostasis in the brain microenvironment;however,the molecular mechanisms underlying the formation and function of the blood-brain barrier remain poorly understood.The major facilitator superfamily domain containing 2A has been identified as a key regulator of blood-brain barrier function.It plays a critical role in promoting and maintaining the formation and functional stability of the blood-brain barrier,in addition to the transport of lipids,such as docosahexaenoic acid,across the blood-brain barrier.Furthermore,an increasing number of studies have suggested that major facilitator superfamily domain containing 2A is involved in the molecular mechanisms of blood-brain barrier dysfunction in a variety of neurological diseases;however,little is known regarding the mechanisms by which major facilitator superfamily domain containing 2A affects the blood-brain barrier.This paper provides a comprehensive and systematic review of the close relationship between major facilitator superfamily domain containing 2A proteins and the blood-brain barrier,including their basic structures and functions,cross-linking between major facilitator superfamily domain containing 2A and the blood-brain barrier,and the in-depth studies on lipid transport and the regulation of blood-brain barrier permeability.This comprehensive systematic review contributes to an in-depth understanding of the important role of major facilitator superfamily domain containing 2A proteins in maintaining the structure and function of the blood-brain barrier and the research progress to date.This will not only help to elucidate the pathogenesis of neurological diseases,improve the accuracy of laboratory diagnosis,and optimize clinical treatment strategies,but it may also play an important role in prognostic monitoring.In addition,the effects of major facilitator superfamily domain containing 2A on blood-brain barrier leakage in various diseases and the research progress on cross-blood-brain barrier drug delivery are summarized.This review may contribute to the development of new approaches for the treatment of neurological diseases.
基金supported by grants from Tianjin Natural Scientific Foundation(14JCZDJC32800)National Basic Research Program of China(2015CB553905)+1 种基金Hi-Tech Research and Development Program of China(2014AA020903)The National Natural Science Foundation of China(81372186)~~
