Background: Isoleucine(Ile) has been implicated in the regulation of energy homeostasis and adipogenesis.However,the impact of surplus dietary Ile intake on muscle lipogenesis remains unknown.The present study aimed t...Background: Isoleucine(Ile) has been implicated in the regulation of energy homeostasis and adipogenesis.However,the impact of surplus dietary Ile intake on muscle lipogenesis remains unknown.The present study aimed to investigate the impact of dietary supplementation of extra-Ile on lipogenesis,fatty acid profile and lipid accumulation in skeletal muscle in finishing pigs.Methods: Forty-eight barrows with initial body weight of 77.0 ± 0.1 kg were allotted to one of two groups and fed diets containing 0.39%,0.53% standardized ileal digestible(SID) Ile with six replicates per treatment and four pigs per replicate for 30 d.Results: Dietary Ile intake significantly improved the intramuscular fat(IMF) content and monounsaturated fatty acid(MUFA) concentration in the skeletal muscle(P < 0.05),and decreased the drip loss and shear force(P < 0.05) without influencing the growth performance of pigs(P > 0.05).Moreover,the phosphorylation of adenosine monophosphate activated protein kinase α(AMPKα) and acetyl coenzyme A carboxylase(ACC) proteins that monitor lipid metabolism were decreased in skeletal muscle of pigs offered extra-Ile diet(P < 0.05).The mRNA expression of adipose-specific genes adipocyte determination and differentiation factor 1(ADD1),fatty acid synthase(FAS),and stearoyl-CoA desaturase(SCD) were upregulated and the activity of SCD was increased as well(P < 0.05).Conclusions: Surplus dietary Ile intake could increase IMF accumulation and MUFA synthesis in skeletal muscle through depressing the phosphorylation of AMPKα-ACC and stimulating the expression and activity of SCD,and increasing the capability of lipogenesis in skeletal muscle.展开更多
Vacuum ultraviolet photon-induced ionization and dissociation of isoleucine are investi- gated with synchrotron radiation photoionization mass spectroscopy and theoretical cal- culations. The main fragment ions at m/z...Vacuum ultraviolet photon-induced ionization and dissociation of isoleucine are investi- gated with synchrotron radiation photoionization mass spectroscopy and theoretical cal- culations. The main fragment ions at m/z=86, 75, 74, 69, 57, 46, 45, 44, 41, 30, 28, and 18 from isoleucine are observed in the mass spectrum at the photon energy of 13 eV. From the photoionization efficiency curves, appearance energies for the principal fragment ions CsH12N+ (rn/z=86), C2H5NO2+ (m/z=75), C5H9+ (rn/z=-69), C4H9+ (m/z=57), and CH4N+ (m/z=30) are determined to be 8.844-0.07, 9.254-0.06, 10.20-4-0.12, 9.254-0.10, and 11.05+0.07 eV, respectively, and possible formation pathways are established in detail by the calculations at the B3LYP/6-31++G(d, p) levels. These proposed channels include simple bond cleavage reactions as well as reactions involving intermediates and transition structures. The experimental and computational appearance energies or barriers are in good agreement.展开更多
Background:Muscle is the complex and heterogeneous tissue,which comprises the primary edible part of the trunk of fish and mammals.Previous studies have shown that dietary isoleucine(Ile)exerts beneficial effects on g...Background:Muscle is the complex and heterogeneous tissue,which comprises the primary edible part of the trunk of fish and mammals.Previous studies have shown that dietary isoleucine(Ile)exerts beneficial effects on growth in aquatic animals.However,there were limited studies regarding the benefits of Ile on fish muscle and their effects on flesh quality and muscle growth.Thus,this study was conducted to explore whether dietary Ile had affected flesh quality and muscle growth in hybrid bagrid catfish(Pelteobagrus vachelli♀×Leiocassis longirostris♂).Methods:A total of 630 hybrid fish,with an initial average body weight of 33.11±0.09 g,were randomly allotted into seven experimental groups with three replicates each,and respectively fed seven diets with 5.0,7.5,10.0,12.5,15.0,17.5,and 20.0 g Ile/kg diets for 8 weeks.Results:In the present study,we demonstrated that Ile significantly:(1)increased muscle protein and lipid contents and the frequency distribution of myofibers with≤20μm and≥50μm of diameter;(2)improved pH value,shear force,cathepsin B and L activities,hydroxyproline content,resilience,cohesiveness,and decreased cooking loss,lactate content,hardness,springiness,gumminess,and chewiness;(3)decreased reactive oxygen species(ROS),malondialdehyde(MDA),and protein carbonyl(PC)contents,GCLC and Keap1 mRNA levels,and up-regulated CuZnSOD,CAT,GPX1a,GST,and Nrf2 mRNA levels;(4)up-regulated the insulin-like growth factor 1,2(IGF-1,IGF-2),insulin-like growth factor 1 receptor(IGF-1R),proliferating cell nuclear antigen(PCNA),Myf5,Myod,Myog,Mrf4,and MyHC mRNA levels,and decreased MSTN mRNAlevel;(5)increased muscle protein deposition by activating AKT-TOR-S6K1 and AKT-FOXO3a signaling pathways.Conclusion:These results revealed that dietary Ile improved flesh quality,which might be due to increasing nutritional content,physicochemical,texture parameters,and antioxidant ability;promoting muscle growth by affecting myocytes hyperplasia and hypertrophy,and muscle protein deposition associated with protein synthesis and degradation signaling pathways.Finally,the quadratic regression analysis of chewiness,ROS,and protein contents against dietary Ile levels suggested that the optimal dietary Ile levels for hybrid bagrid catfish was estimated to be 14.19,12.36,and 12.78 g/kg diet,corresponding to 36.59,31.87,and 32.96 g/kg dietary protein,respectively.展开更多
Anti-microbial peptides are essential for the intestinal innate immunity that protects the intestinal epithelia from attacks by foreign pathogens. Human β-defensin (HBD) is one of the pivotal anti-microbial peptides ...Anti-microbial peptides are essential for the intestinal innate immunity that protects the intestinal epithelia from attacks by foreign pathogens. Human β-defensin (HBD) is one of the pivotal anti-microbial peptides that are expressed in the colonic epithelia. This study investigated the effect and the signaling mechanism of inducible β-defensin HBD2 by an essential amino acid, isoleucine (Ile) in colonic epithelial cells. Here we examined the expression level of HBD2 on induction of Ile in epithelial cells, and checked this pathway. HBD2 mRNA was induced by co-incubation with IL-1α and Ile in Caco2 cells, but not by Ile alone. An inhibitor of either ERK or Gi, a subunit of G-proteins, reduced the induction of HBD2 mRNA by Ile. The treatment with Ile also increased the intracellular calcium ion concentration, thus suggesting that the GPCR and ERK signaling pathway mediate the effects of Ile. These results indicate that an essential amino acid, Ile, enhances the expression of an inducible β-defensin, namely HBD2, by IL-1α through the activation of GPCRs and ERK signaling pathway. The administration of Ile may therefore represent a possible option to safely treat intestinal inflammation.展开更多
The thought of using branched-chain amino acids (BCAA) in the prevention and treatment of certain disorders is becoming increasingly popular. Individual BCAA use has been associated with improving glucose tolerance an...The thought of using branched-chain amino acids (BCAA) in the prevention and treatment of certain disorders is becoming increasingly popular. Individual BCAA use has been associated with improving glucose tolerance and liver disease. Previous studies have cited improvements in glucose metabolism with a single dose of L-isoleucine (ILE). However, it is still unclear whether chronic consumption of ILE has any direct benefit. The objective of this study was to examine the influence of chronic ILE supplementation alone or in combination with exercise on fasting serum glucose, insulin, lipids, and lipoprotein cholesterol levels;glucose tolerance;and hepatic lipids in rats. Male Sprague-Dawley rats (n = 40) were divided into Control (low fructose diet);High Fructose diet (HF);HF plus 1.5% ILE (HF + ILE);HF plus exercise (HF + EX);and HF plus 1.5% ILE and exercise (HF + ILE + EX). The HF diets consisted of 70% kcalories from fructose. After 6 weeks of treatment, no significant differences were observed between groups for changes in fasting serum glucose, insulin, lipids, or lipoprotein cholesterol levels. However, hepatic total cholesterol was significantly lower in the HF + ILE + EX compared to the Control and HF, while, the HF + ILE had significantly lower hepatic free cholesterol compared to the HF. We also found no differences between groups for serum glucose response following an oral glucose tolerance test. In conclusion, our study shows that ILE supplementation in rats does not influence serum glucose and lipid biomarkers but may have an influence on lipid metabolic pathways within the liver.展开更多
The aim of the present investigation was to develop a biosensor for the detection of amino acids, Leucine, Isoleucine and Valine based on a quartz crystal nanobalance. leucine (Leu), isoleucine (Ile), and valine (Val)...The aim of the present investigation was to develop a biosensor for the detection of amino acids, Leucine, Isoleucine and Valine based on a quartz crystal nanobalance. leucine (Leu), isoleucine (Ile), and valine (Val) were selectively determined by quartz crystal nanobalance (QCN) sensor in conjunction with net analyte signal (NAS)-based method called HLA/GO. An orthogonal design was applied for the formation of calibration and prediction sets including Leu, Ile and Val compounds. The selection of the optimal time range involved the calculation of the net analyte sig-nal regression plot in any considered time window for each test sample. The searching of a region with maximum linearity of NAS regression plot (minimum error indicator) and minimum of PRESS value was carried out by applying a moving window strategy. On the base of obtained results, the differences on the adsorption profiles in the time range between 1 and 300 s were used to determine mixtures of compounds by HLA/GO method. The results showed that the method was successfully applied for the determina-tion of Leu, Ile and Val.展开更多
A series of new optically active aromatic poly(ester amide)s containing a chiral group in the side chain prepared from the p-toluenesulfonic acid salt of o,o'-bis(leucyl)-hexanediol (TS-+LHD+TS-) and p-phthaloyl c...A series of new optically active aromatic poly(ester amide)s containing a chiral group in the side chain prepared from the p-toluenesulfonic acid salt of o,o'-bis(leucyl)-hexanediol (TS-+LHD+TS-) and p-phthaloyl chloride and styrene-2,5- dicarbonyl chloride styrene have been synthesized by interfacial polymerization. The structure of the monomer is elucidated by FT-IR and elemental analysis. The thermal properties of the polymers were studied by DSC and TGA. The chiroptical properties of the above polymer have also been studied by circular dichroism (CD) spectroscopy. Results indicated that these polymers form helical structures.展开更多
The diffusion coefficients of aqueous solutions ofglycine, L-alanine, L-valine and L-isoleucine at 298.15 K were determined by holographic interferometry with accuracy and promptness while without disturbance. The den...The diffusion coefficients of aqueous solutions ofglycine, L-alanine, L-valine and L-isoleucine at 298.15 K were determined by holographic interferometry with accuracy and promptness while without disturbance. The density and viscosity of these solutions were also determined. According to original Gordon model, a model for correlating the diffusion coefficients of amino acids in aqueous solutions was developed and applied. The results showed that this model provided significant convenience in correlation of diffusion coefficients for amino acids system.展开更多
TAU is a microtubule-associated protein that promotes microtubule assembly and stability in the axon.TAU is missorted and aggregated in an array of diseases known as tauopathies.Microtubules are essential for neuronal...TAU is a microtubule-associated protein that promotes microtubule assembly and stability in the axon.TAU is missorted and aggregated in an array of diseases known as tauopathies.Microtubules are essential for neuronal function and regulated via a complex set of post-translational modifications,changes of which affect microtubule stability and dynamics,microtubule interaction with other proteins and cellular structures,and mediate recruitment of microtubule-severing enzymes.As impairment of microtubule dynamics causes neuronal dysfunction,we hypothesize cognitive impairment in human disease to be impacted by impairment of microtubule dynamics.We therefore aimed to study the effects of a disease-causing mutation of TAU(P301L)on the levels and localization of microtubule post-translational modifications indicative of microtubule stability and dynamics,to assess whether P301L-TAU causes stability-changing modifications to microtubules.To investigate TAU localization,phosphorylation,and effects on tubulin post-translational modifications,we expressed wild-type or P301L-TAU in human MAPT-KO induced pluripotent stem cell-derived neurons(i Neurons)and studied TAU in neurons in the hippocampus of mice transgenic for human P301L-TAU(p R5 mice).Human neurons expressing the longest TAU isoform(2N4R)with the P301L mutation showed increased TAU phosphorylation at the AT8,but not the p-Ser-262 epitope,and increased polyglutamylation and acetylation of microtubules compared with endogenous TAU-expressing neurons.P301L-TAU showed pronounced somatodendritic presence,but also successful axonal enrichment and a similar axodendritic distribution comparable to exogenously expressed 2N4R-wildtype-TAU.P301L-TAU-expressing hippocampal neurons in transgenic mice showed prominent missorting and tauopathy-typical AT8-phosphorylation of TAU and increased polyglutamylation,but reduced acetylation,of microtubules compared with non-transgenic littermates.In sum,P301L-TAU results in changes in microtubule PTMs,suggestive of impairment of microtubule stability.This is accompanied by missorting and aggregation of TAU in mice but not in i Neurons.Microtubule PTMs/impairment may be of key importance in tauopathies.展开更多
Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life ...Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of patients.To date,there are no viable treatment options for postoperative cognitive dysfunction.The identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future research.To identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial fracture.The dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub gene.Therefore,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re surgery.Mice were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning tests.In addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western blotting.Treatment with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expression compared with vehicle treatment.Intraperitoneal administration of the specific ERK inhibitor PD98059 diminished the effects of recombinant chitinase-3-like protein 1.Collectively,our findings suggest that recombinant chitinase-3-like protein 1 ameliorates surgery-induced cognitive decline by attenuating neuroinflammation via M2 microglial polarization in the hippocampus.Therefore,recombinant chitinase-3-like protein1 may have therapeutic potential fo r postoperative cognitive dysfunction.展开更多
We performed a PubMed search for microRNAs in autism spectrum disorder that could serve as diagnostic biomarkers in patients and selected 17 articles published from January 2008 to December 2023,of which 4 studies wer...We performed a PubMed search for microRNAs in autism spectrum disorder that could serve as diagnostic biomarkers in patients and selected 17 articles published from January 2008 to December 2023,of which 4 studies were performed with whole blood,4 with blood plasma,5 with blood serum,1 with serum neural cell adhesion molecule L1-captured extracellular vesicles,1 with blood cells,and 2 with peripheral blood mononuclear cells.Most of the studies involved children and the study cohorts were largely males.Many of the studies had performed microRNA sequencing or quantitative polymerase chain reaction assays to measure microRNA expression.Only five studies had used real-time polymerase chain reaction assay to validate microRNA expression in autism spectrum disorder subjects compared to controls.The microRNAs that were validated in these studies may be considered as potential candidate biomarkers for autism spectrum disorder and include miR-500a-5p,-197-5p,-424-5p,-664a-3p,-365a-3p,-619-5p,-664a-3p,-3135a,-328-3p,and-500a-5p in blood plasma and miR-151a-3p,-181b-5p,-320a,-328,-433,-489,-572,-663a,-101-3p,-106b-5p,-19b-3p,-195-5p,and-130a-3p in blood serum of children,and miR-15b-5p and-6126 in whole blood of adults.Several important limitations were identified in the studies reviewed,and need to be taken into account in future studies.Further studies are warranted with children and adults having different levels of autism spectrum disorder severity and consideration should be given to using animal models of autism spectrum disorder to investigate the effects of suppressing or overexpressing specific microRNAs as a novel therapy.展开更多
基金supported by the National Key Research and Development Program of China(2018YFD0500402)the National Natural Science Foundation of China(No.31672431)the National Key Research and Development Program(2016YFD0700201)
文摘Background: Isoleucine(Ile) has been implicated in the regulation of energy homeostasis and adipogenesis.However,the impact of surplus dietary Ile intake on muscle lipogenesis remains unknown.The present study aimed to investigate the impact of dietary supplementation of extra-Ile on lipogenesis,fatty acid profile and lipid accumulation in skeletal muscle in finishing pigs.Methods: Forty-eight barrows with initial body weight of 77.0 ± 0.1 kg were allotted to one of two groups and fed diets containing 0.39%,0.53% standardized ileal digestible(SID) Ile with six replicates per treatment and four pigs per replicate for 30 d.Results: Dietary Ile intake significantly improved the intramuscular fat(IMF) content and monounsaturated fatty acid(MUFA) concentration in the skeletal muscle(P < 0.05),and decreased the drip loss and shear force(P < 0.05) without influencing the growth performance of pigs(P > 0.05).Moreover,the phosphorylation of adenosine monophosphate activated protein kinase α(AMPKα) and acetyl coenzyme A carboxylase(ACC) proteins that monitor lipid metabolism were decreased in skeletal muscle of pigs offered extra-Ile diet(P < 0.05).The mRNA expression of adipose-specific genes adipocyte determination and differentiation factor 1(ADD1),fatty acid synthase(FAS),and stearoyl-CoA desaturase(SCD) were upregulated and the activity of SCD was increased as well(P < 0.05).Conclusions: Surplus dietary Ile intake could increase IMF accumulation and MUFA synthesis in skeletal muscle through depressing the phosphorylation of AMPKα-ACC and stimulating the expression and activity of SCD,and increasing the capability of lipogenesis in skeletal muscle.
基金V. ACKNOWLEDGMENTS This work is supported by the National Natural Science Foundation of China (No.10875126 and No.10979048) and the Specialized Research Fund for the Doctoral Program of Higher Education, SRF for ROCS, SEM.
文摘Vacuum ultraviolet photon-induced ionization and dissociation of isoleucine are investi- gated with synchrotron radiation photoionization mass spectroscopy and theoretical cal- culations. The main fragment ions at m/z=86, 75, 74, 69, 57, 46, 45, 44, 41, 30, 28, and 18 from isoleucine are observed in the mass spectrum at the photon energy of 13 eV. From the photoionization efficiency curves, appearance energies for the principal fragment ions CsH12N+ (rn/z=86), C2H5NO2+ (m/z=75), C5H9+ (rn/z=-69), C4H9+ (m/z=57), and CH4N+ (m/z=30) are determined to be 8.844-0.07, 9.254-0.06, 10.20-4-0.12, 9.254-0.10, and 11.05+0.07 eV, respectively, and possible formation pathways are established in detail by the calculations at the B3LYP/6-31++G(d, p) levels. These proposed channels include simple bond cleavage reactions as well as reactions involving intermediates and transition structures. The experimental and computational appearance energies or barriers are in good agreement.
基金supported by National Key R&D Program of China(2019YFD0900200)the Applied Basic Research Programs of ScienceTechnology Commission Foundation of Sichuan Province,China(2015JY0067).
文摘Background:Muscle is the complex and heterogeneous tissue,which comprises the primary edible part of the trunk of fish and mammals.Previous studies have shown that dietary isoleucine(Ile)exerts beneficial effects on growth in aquatic animals.However,there were limited studies regarding the benefits of Ile on fish muscle and their effects on flesh quality and muscle growth.Thus,this study was conducted to explore whether dietary Ile had affected flesh quality and muscle growth in hybrid bagrid catfish(Pelteobagrus vachelli♀×Leiocassis longirostris♂).Methods:A total of 630 hybrid fish,with an initial average body weight of 33.11±0.09 g,were randomly allotted into seven experimental groups with three replicates each,and respectively fed seven diets with 5.0,7.5,10.0,12.5,15.0,17.5,and 20.0 g Ile/kg diets for 8 weeks.Results:In the present study,we demonstrated that Ile significantly:(1)increased muscle protein and lipid contents and the frequency distribution of myofibers with≤20μm and≥50μm of diameter;(2)improved pH value,shear force,cathepsin B and L activities,hydroxyproline content,resilience,cohesiveness,and decreased cooking loss,lactate content,hardness,springiness,gumminess,and chewiness;(3)decreased reactive oxygen species(ROS),malondialdehyde(MDA),and protein carbonyl(PC)contents,GCLC and Keap1 mRNA levels,and up-regulated CuZnSOD,CAT,GPX1a,GST,and Nrf2 mRNA levels;(4)up-regulated the insulin-like growth factor 1,2(IGF-1,IGF-2),insulin-like growth factor 1 receptor(IGF-1R),proliferating cell nuclear antigen(PCNA),Myf5,Myod,Myog,Mrf4,and MyHC mRNA levels,and decreased MSTN mRNAlevel;(5)increased muscle protein deposition by activating AKT-TOR-S6K1 and AKT-FOXO3a signaling pathways.Conclusion:These results revealed that dietary Ile improved flesh quality,which might be due to increasing nutritional content,physicochemical,texture parameters,and antioxidant ability;promoting muscle growth by affecting myocytes hyperplasia and hypertrophy,and muscle protein deposition associated with protein synthesis and degradation signaling pathways.Finally,the quadratic regression analysis of chewiness,ROS,and protein contents against dietary Ile levels suggested that the optimal dietary Ile levels for hybrid bagrid catfish was estimated to be 14.19,12.36,and 12.78 g/kg diet,corresponding to 36.59,31.87,and 32.96 g/kg dietary protein,respectively.
文摘Anti-microbial peptides are essential for the intestinal innate immunity that protects the intestinal epithelia from attacks by foreign pathogens. Human β-defensin (HBD) is one of the pivotal anti-microbial peptides that are expressed in the colonic epithelia. This study investigated the effect and the signaling mechanism of inducible β-defensin HBD2 by an essential amino acid, isoleucine (Ile) in colonic epithelial cells. Here we examined the expression level of HBD2 on induction of Ile in epithelial cells, and checked this pathway. HBD2 mRNA was induced by co-incubation with IL-1α and Ile in Caco2 cells, but not by Ile alone. An inhibitor of either ERK or Gi, a subunit of G-proteins, reduced the induction of HBD2 mRNA by Ile. The treatment with Ile also increased the intracellular calcium ion concentration, thus suggesting that the GPCR and ERK signaling pathway mediate the effects of Ile. These results indicate that an essential amino acid, Ile, enhances the expression of an inducible β-defensin, namely HBD2, by IL-1α through the activation of GPCRs and ERK signaling pathway. The administration of Ile may therefore represent a possible option to safely treat intestinal inflammation.
文摘The thought of using branched-chain amino acids (BCAA) in the prevention and treatment of certain disorders is becoming increasingly popular. Individual BCAA use has been associated with improving glucose tolerance and liver disease. Previous studies have cited improvements in glucose metabolism with a single dose of L-isoleucine (ILE). However, it is still unclear whether chronic consumption of ILE has any direct benefit. The objective of this study was to examine the influence of chronic ILE supplementation alone or in combination with exercise on fasting serum glucose, insulin, lipids, and lipoprotein cholesterol levels;glucose tolerance;and hepatic lipids in rats. Male Sprague-Dawley rats (n = 40) were divided into Control (low fructose diet);High Fructose diet (HF);HF plus 1.5% ILE (HF + ILE);HF plus exercise (HF + EX);and HF plus 1.5% ILE and exercise (HF + ILE + EX). The HF diets consisted of 70% kcalories from fructose. After 6 weeks of treatment, no significant differences were observed between groups for changes in fasting serum glucose, insulin, lipids, or lipoprotein cholesterol levels. However, hepatic total cholesterol was significantly lower in the HF + ILE + EX compared to the Control and HF, while, the HF + ILE had significantly lower hepatic free cholesterol compared to the HF. We also found no differences between groups for serum glucose response following an oral glucose tolerance test. In conclusion, our study shows that ILE supplementation in rats does not influence serum glucose and lipid biomarkers but may have an influence on lipid metabolic pathways within the liver.
文摘The aim of the present investigation was to develop a biosensor for the detection of amino acids, Leucine, Isoleucine and Valine based on a quartz crystal nanobalance. leucine (Leu), isoleucine (Ile), and valine (Val) were selectively determined by quartz crystal nanobalance (QCN) sensor in conjunction with net analyte signal (NAS)-based method called HLA/GO. An orthogonal design was applied for the formation of calibration and prediction sets including Leu, Ile and Val compounds. The selection of the optimal time range involved the calculation of the net analyte sig-nal regression plot in any considered time window for each test sample. The searching of a region with maximum linearity of NAS regression plot (minimum error indicator) and minimum of PRESS value was carried out by applying a moving window strategy. On the base of obtained results, the differences on the adsorption profiles in the time range between 1 and 300 s were used to determine mixtures of compounds by HLA/GO method. The results showed that the method was successfully applied for the determina-tion of Leu, Ile and Val.
基金This work was supported by the National Natural Science Foundation of China (No. 20134010,20274003).
文摘A series of new optically active aromatic poly(ester amide)s containing a chiral group in the side chain prepared from the p-toluenesulfonic acid salt of o,o'-bis(leucyl)-hexanediol (TS-+LHD+TS-) and p-phthaloyl chloride and styrene-2,5- dicarbonyl chloride styrene have been synthesized by interfacial polymerization. The structure of the monomer is elucidated by FT-IR and elemental analysis. The thermal properties of the polymers were studied by DSC and TGA. The chiroptical properties of the above polymer have also been studied by circular dichroism (CD) spectroscopy. Results indicated that these polymers form helical structures.
基金Supported by the National 973 Program of China (No. 2003CB615701)the National 863 Project of China (No. 2003AA328020)the National Natural Science Foundation of China (No. 200276034)the Educational Ministry Doctor Foundation of China (No 2000005608).
文摘The diffusion coefficients of aqueous solutions ofglycine, L-alanine, L-valine and L-isoleucine at 298.15 K were determined by holographic interferometry with accuracy and promptness while without disturbance. The density and viscosity of these solutions were also determined. According to original Gordon model, a model for correlating the diffusion coefficients of amino acids in aqueous solutions was developed and applied. The results showed that this model provided significant convenience in correlation of diffusion coefficients for amino acids system.
基金supported by the Koeln Fortune Program/Faculty of Medicine,University of Cologne,the Alzheimer Forschung Initiative e.V.(grant#22039,to HZ)open-access funding from the DFG/GRC issued to the University of CologneAlzheimer Forschung Initiative e.V.for Open Access Publishing(a publication grant#P2401,to MAAK)。
文摘TAU is a microtubule-associated protein that promotes microtubule assembly and stability in the axon.TAU is missorted and aggregated in an array of diseases known as tauopathies.Microtubules are essential for neuronal function and regulated via a complex set of post-translational modifications,changes of which affect microtubule stability and dynamics,microtubule interaction with other proteins and cellular structures,and mediate recruitment of microtubule-severing enzymes.As impairment of microtubule dynamics causes neuronal dysfunction,we hypothesize cognitive impairment in human disease to be impacted by impairment of microtubule dynamics.We therefore aimed to study the effects of a disease-causing mutation of TAU(P301L)on the levels and localization of microtubule post-translational modifications indicative of microtubule stability and dynamics,to assess whether P301L-TAU causes stability-changing modifications to microtubules.To investigate TAU localization,phosphorylation,and effects on tubulin post-translational modifications,we expressed wild-type or P301L-TAU in human MAPT-KO induced pluripotent stem cell-derived neurons(i Neurons)and studied TAU in neurons in the hippocampus of mice transgenic for human P301L-TAU(p R5 mice).Human neurons expressing the longest TAU isoform(2N4R)with the P301L mutation showed increased TAU phosphorylation at the AT8,but not the p-Ser-262 epitope,and increased polyglutamylation and acetylation of microtubules compared with endogenous TAU-expressing neurons.P301L-TAU showed pronounced somatodendritic presence,but also successful axonal enrichment and a similar axodendritic distribution comparable to exogenously expressed 2N4R-wildtype-TAU.P301L-TAU-expressing hippocampal neurons in transgenic mice showed prominent missorting and tauopathy-typical AT8-phosphorylation of TAU and increased polyglutamylation,but reduced acetylation,of microtubules compared with non-transgenic littermates.In sum,P301L-TAU results in changes in microtubule PTMs,suggestive of impairment of microtubule stability.This is accompanied by missorting and aggregation of TAU in mice but not in i Neurons.Microtubule PTMs/impairment may be of key importance in tauopathies.
基金supported by the National Natural Science Foundation of China,Nos.81730033,82171193(to XG)the Key Talent Project for Strengthening Health during the 13^(th)Five-Year Plan Period,No.ZDRCA2016069(to XG)+1 种基金the National Key R&D Program of China,No.2018YFC2001901(to XG)Jiangsu Provincial Medical Key Discipline,No.ZDXK202232(to XG)。
文摘Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of patients.To date,there are no viable treatment options for postoperative cognitive dysfunction.The identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future research.To identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial fracture.The dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub gene.Therefore,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re surgery.Mice were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning tests.In addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western blotting.Treatment with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expression compared with vehicle treatment.Intraperitoneal administration of the specific ERK inhibitor PD98059 diminished the effects of recombinant chitinase-3-like protein 1.Collectively,our findings suggest that recombinant chitinase-3-like protein 1 ameliorates surgery-induced cognitive decline by attenuating neuroinflammation via M2 microglial polarization in the hippocampus.Therefore,recombinant chitinase-3-like protein1 may have therapeutic potential fo r postoperative cognitive dysfunction.
文摘We performed a PubMed search for microRNAs in autism spectrum disorder that could serve as diagnostic biomarkers in patients and selected 17 articles published from January 2008 to December 2023,of which 4 studies were performed with whole blood,4 with blood plasma,5 with blood serum,1 with serum neural cell adhesion molecule L1-captured extracellular vesicles,1 with blood cells,and 2 with peripheral blood mononuclear cells.Most of the studies involved children and the study cohorts were largely males.Many of the studies had performed microRNA sequencing or quantitative polymerase chain reaction assays to measure microRNA expression.Only five studies had used real-time polymerase chain reaction assay to validate microRNA expression in autism spectrum disorder subjects compared to controls.The microRNAs that were validated in these studies may be considered as potential candidate biomarkers for autism spectrum disorder and include miR-500a-5p,-197-5p,-424-5p,-664a-3p,-365a-3p,-619-5p,-664a-3p,-3135a,-328-3p,and-500a-5p in blood plasma and miR-151a-3p,-181b-5p,-320a,-328,-433,-489,-572,-663a,-101-3p,-106b-5p,-19b-3p,-195-5p,and-130a-3p in blood serum of children,and miR-15b-5p and-6126 in whole blood of adults.Several important limitations were identified in the studies reviewed,and need to be taken into account in future studies.Further studies are warranted with children and adults having different levels of autism spectrum disorder severity and consideration should be given to using animal models of autism spectrum disorder to investigate the effects of suppressing or overexpressing specific microRNAs as a novel therapy.