Diabetic peripheral neuropathy is a common complication of diabetes mellitus.Elucidating the pathophysiological metabolic mechanism impels the generation of ideal therapies.However,existing limited treatments for diab...Diabetic peripheral neuropathy is a common complication of diabetes mellitus.Elucidating the pathophysiological metabolic mechanism impels the generation of ideal therapies.However,existing limited treatments for diabetic peripheral neuropathy expose the urgent need for cell metabolism research.Given the lack of comprehensive understanding of energy metabolism changes and related signaling pathways in diabetic peripheral neuropathy,it is essential to explore energy changes and metabolic changes in diabetic peripheral neuropathy to develop suitable treatment methods.This review summarizes the pathophysiological mechanism of diabetic peripheral neuropathy from the perspective of cellular metabolism and the specific interventions for different metabolic pathways to develop effective treatment methods.Various metabolic mechanisms(e.g.,polyol,hexosamine,protein kinase C pathway)are associated with diabetic peripheral neuropathy,and researchers are looking for more effective treatments through these pathways.展开更多
The mammary gland tissue exhibits a series of responses that are different from those of muscle and other peripheral tissues under amino acid deficiency. So, this present study was designed to investigate the effects ...The mammary gland tissue exhibits a series of responses that are different from those of muscle and other peripheral tissues under amino acid deficiency. So, this present study was designed to investigate the effects of amino acid nutritional deficiency on the expression of protein metabolism-related genes in the mammary gland and muscle tissues of lactating mice. A total of 60 postpartum, lactating Kunming white mice were selected and randomly divided into 5 groups;each group contained 12 mice. Group A was the control group. The mice in group A were maintained on a normal diet after the initiation of lactation. Group B (starved) was given normal saline via intragastric administration. Group C (energy) was given glucose solution via intragastric administration. Groups D and E received a sodium caseinate solution via intragastric administration, which provided 0.5 g protein/d and 1.5 g protein/d, respectively. The results showed the following. 1) When the mice were exposed to nutritional stress caused by dietary amino acid deficiency, the β-casein mRNA expression level was increased in the mammary gland tissue. The increase in β-casein expression was the most significant in the energy-supplemented group, followed by the starved group (P P 14k and C2 (P P P < 0.05). 5) The phosphorylation level of p70S6K was elevated in the muscle tissues collected from the treatment groups. However, the magnitude of the increase was far smaller compared to that in the mammary gland tissues.展开更多
Growth-associated protein 43 plays a key role in neurite outgrowth through cytoskeleton remodeling.We have previously demonstrated that structural damage of peripheral nerves induces growth-associated protein 43 upreg...Growth-associated protein 43 plays a key role in neurite outgrowth through cytoskeleton remodeling.We have previously demonstrated that structural damage of peripheral nerves induces growth-associated protein 43 upregulation to promote growth cone formation.Conversely,the limited regenerative capacity of the central nervous system due to an inhibitory environment prevents major changes in neurite outgrowth and should be presumably associated with low levels of growth-associated protein 43 expression.However,central alterations due to peripheral nerve damage have never been assessed using the growthassociated protein 43 marker.In this study,we used the tubulization technique to repair 1 cm-long nerve gaps in the rat nerve injury/repair model and detected growth-associated protein 43 expression in the peripheral and central nervous systems.First,histological analysis of the regeneration process confirmed an active regeneration process of the nerve gaps through the conduit from 10 days onwards.The growth-associated protein 43 expression profile varied across regions and follow-up times,from a localized expression to an abundant and consistent expression throughout the regeneration tissue,confirming the presence of an active nerve regeneration process.Second,spinal cord changes were also histologically assessed,and no apparent changes in the structural and cellular organization were observed using routine staining methods.Surprisingly,remarkable differences and local changes appeared in growth-associated protein 43 expression at the spinal cord level,in particular at 20 days post-repair and beyond.Growth-associated protein 43 protein was first localized in the gracile fasciculus and was homogeneously distributed in the left posterior cord.These findings differed from the growth-associated protein 43 pattern observed in the healthy control,which did not express growth-associated protein 43 at these levels.Our results revealed a differential expression in growth-associated protein 43 protein not only in the regenerating nerve tissue but also in the spinal cord after peripheral nerve transection.These findings open the possibility of using this marker to monitor changes in the central nervous system after peripheral nerve injury.展开更多
BACKGROUND Perinatal exposure to a poor nutritional environment predisposes the progeny to the development of metabolic disease at the adult age,both in experimental models and humans.Numerous adaptive responses to ma...BACKGROUND Perinatal exposure to a poor nutritional environment predisposes the progeny to the development of metabolic disease at the adult age,both in experimental models and humans.Numerous adaptive responses to maternal protein restriction have been reported in metabolic tissues.However,the expression of glucose/fatty acid metabolism-related genes in adipose tissue and liver needs to be described.AIM To evaluate the metabolic impact of perinatal malnutrition,we determined malnutrition-associated gene expression alterations in liver and adipose tissue.METHODS In the present study,we evaluated the alterations in gene expression of glycolytic/Krebs cycle genes(Pyruvate dehydrogenase kinase 4 and citrate synthase),adipogenic and lipolytic genes and leptin in the adipose tissue of offspring rats at 30 d and 90 d of age exposed to maternal isocaloric low protein(LP)diet throughout gestation and lactation.We also evaluated,in the livers of the same animals,the same set of genes as well as the gene expression of the transcription factors peroxisome proliferator-activated receptor gamma coactivator 1,forkhead box protein O1 and hepatocyte nuclear factor 4 and of gluconeogenic genes.RESULTS In the adipose tissue,we observed a transitory(i.e.,at 30 d)downregulation of pyruvate dehydrogenase kinase 4,citrate synthase and carnitine palmitoyl transferase 1b gene expression.Such transcriptional changes did not persist in adult LP rats(90 d),but we observed a tendency towards a decreased gene expression of leptin(P=0.052).The liver featured some gene expression alterations comparable to the adipose tissue,such as pyruvate dehydrogenase kinase 4 downregulation at 30 d and displayed other tissue-specific changes,including citrate synthase and fatty acid synthase upregulation,but pyruvate kinase downregulation at 30 d in the LP group and carnitine palmitoyl transferase 1b downregulation at 90 d.These gene alterations,together with previously described changes in gene expression in skeletal muscle,may account for the metabolic adaptations in response to maternal LP diet and highlight the occurrence of persistent transcriptional defects in key metabolic genes that may contribute to the development of metabolic alterations during the adult life as a consequence of perinatal malnutrition.CONCLUSION We conclude that perinatal malnutrition relays long-lasting transcriptional alterations in metabolically active organs,i.e.,liver and adipose tissue.展开更多
This experiment was conducted to investigate the effects of branched-chain amino acids(BCAA)supplemented in protein-restricted diets on the growth performance and the expression profile of amino acid transporters and ...This experiment was conducted to investigate the effects of branched-chain amino acids(BCAA)supplemented in protein-restricted diets on the growth performance and the expression profile of amino acid transporters and energy metabolism related regulators in the white adipose tissue(WAT)of different regional depots including dorsal subcutaneous adipose(DSA) and abdominal subcutaneous adipose(ASA), A total of 24 crossbred barrows(7.40 ± 0.70 kg) were randomly divided into 4 groups and were fed the following isocaloric diets for 33 days: 1) a recommended adequate protein diet(AP, 20% CP, as a positive control); 2) a low protein diet(LP, 17% CP); 3) the LP diet supplemented with BCAA(LP + B, 17% CP) to reach the same level of the AP diet group; 4) the LP diet supplemented with 2 times the amount of BCAA(LP + 2B, 17% CP). The daily gain and daily feed intake of the LP diet group were the lowest among all the treatments(P < 0.01). The feed conversion was improved markedly in the group of LP + B compared with the LP diet group(P < 0.05). No significant difference was noted for the serum biochemical parameter concentrations of glucose, triglyceride, nonesterified fatty acid and insulin among the groups(P > 0.05). Moreover, BCAA supplementation down-regulated the expression levels of amino acid transporters including L-type amino acid transporter 1 and sodium-coupled neutral amino acid transporter 2 in DSA, but up-regulated the expression level of Ltype amino acid transporter 4 in ASA(P < 0.05), Meanwhile, the energy sensor AMP-activated protein kinase α was activated in the DSA of pigs fed LP diet and in the ASA of the pigs fed AP or LP + 2B diets(P < 0.05). The mRNA expression profile of the selected mitochondrial component and mitochondrial biogenesis associated regulators in DSA and ASA also responded differently to dietary BCAA supplementation. These results suggested that the growth performance of growing pigs fed protein restricted diets supplemented with BCAA could catch up to that of the pigs fed AP diets. The results also partly demonstrated that the regulation mechanisms of BCAA are different in the adipose tissues of different depots.展开更多
Repetitive transcranial magnetic stimulation （rTMS） has been utilized as a therapeutic tool for neurodegenerative disorders including Alzheimer＇s disease. However, the precise mechanisms of its clinical effects rem...Repetitive transcranial magnetic stimulation （rTMS） has been utilized as a therapeutic tool for neurodegenerative disorders including Alzheimer＇s disease. However, the precise mechanisms of its clinical effects remain unknown. β-amyloid （Aβ） exhibits direct neurotoxic effects and is closely related to neuronal degeneration in Alzheimer＇s disease. Therefore, it has been hypothesized that the neuroprotective effects of rTMS are related to the mechanisms of protection against Aβ neurotoxicity. Organotypic hippocampal slices were prepared from 8-day old, Sprague Dawley rats. The tissue slices were exposed to 100 μmol/L Al3142 since day 12 in vitro with and without high-frequency （20 Hz） magnetic stimulation. Magnetic stimulation efficacy was evaluated by measuring neuronal nuclei （NeuN） protein expression and by observing cultures following propidium iodide fluorescence staining and bromodeoxyuridine （BrdU） immunohistochemistry. Lactate dehydrogenase activity was detected in the culture media to evaluate hippocampal neuronal damage. Our results demonstrated that high-frequency magnetic stimulation significantly reversed the reduction of NeuN protein expression because of Aβ1-42 exposure （P 〈 0.05） and significantly reduced the number of damaged cells in the hippocampal slices （P 〈 0.05）. However, lactate dehydrogenase levels and anti-BrdU staining results did not reveal any statistical differences These findings indicate that high-frequency magnetic stimulation might have protective effect on hippocampal neurons from Aβ1-42 neurotoxicity.展开更多
基金supported by the Projects of the National Key R&D Program of China,Nos.2021YFC2400803(to YO),2021YFC2400801(to YQ)the National Natural Science Foundation of China,Nos.82002290(to YQ),82072452(to YO),82272475(to YO)+5 种基金the Young Elite Scientist Sponsorship Program by Cast,No.YESS20200153(to YQ)the Sino-German Mobility Programme,No.M-0699(to YQ)the Excellent Youth Cultivation Program of Shanghai Sixth People’s Hospital,No.ynyq202201(to YQ)the Shanghai Sailing Program,No.20YF1436000(to YQ)the Medical Engineering Co-Project of University of Shanghai for Science and Technology,10-22-310-520(to YO)a grant from Shanghai Municipal Health Commission,No.202040399(to YO).
文摘Diabetic peripheral neuropathy is a common complication of diabetes mellitus.Elucidating the pathophysiological metabolic mechanism impels the generation of ideal therapies.However,existing limited treatments for diabetic peripheral neuropathy expose the urgent need for cell metabolism research.Given the lack of comprehensive understanding of energy metabolism changes and related signaling pathways in diabetic peripheral neuropathy,it is essential to explore energy changes and metabolic changes in diabetic peripheral neuropathy to develop suitable treatment methods.This review summarizes the pathophysiological mechanism of diabetic peripheral neuropathy from the perspective of cellular metabolism and the specific interventions for different metabolic pathways to develop effective treatment methods.Various metabolic mechanisms(e.g.,polyol,hexosamine,protein kinase C pathway)are associated with diabetic peripheral neuropathy,and researchers are looking for more effective treatments through these pathways.
文摘The mammary gland tissue exhibits a series of responses that are different from those of muscle and other peripheral tissues under amino acid deficiency. So, this present study was designed to investigate the effects of amino acid nutritional deficiency on the expression of protein metabolism-related genes in the mammary gland and muscle tissues of lactating mice. A total of 60 postpartum, lactating Kunming white mice were selected and randomly divided into 5 groups;each group contained 12 mice. Group A was the control group. The mice in group A were maintained on a normal diet after the initiation of lactation. Group B (starved) was given normal saline via intragastric administration. Group C (energy) was given glucose solution via intragastric administration. Groups D and E received a sodium caseinate solution via intragastric administration, which provided 0.5 g protein/d and 1.5 g protein/d, respectively. The results showed the following. 1) When the mice were exposed to nutritional stress caused by dietary amino acid deficiency, the β-casein mRNA expression level was increased in the mammary gland tissue. The increase in β-casein expression was the most significant in the energy-supplemented group, followed by the starved group (P P 14k and C2 (P P P < 0.05). 5) The phosphorylation level of p70S6K was elevated in the muscle tissues collected from the treatment groups. However, the magnitude of the increase was far smaller compared to that in the mammary gland tissues.
基金financed by the Spanish"Plan Nacional de Investigación Cientifica,Desorrollo e Innovación Tecnológica,Ministerio de Economíay Competitividod(Instituto de Solud CarlosⅢ)",grant Nos:FIS PI17-0393,FIS PI20-0318co-financed by the"Fondo Europeo de Desorrollo Regional ERDF-FEDER European Union",grant No.P18-RT-5059+2 种基金by"Plan Andaluz de Investigación,Desarrollo e Innovación(PAIDI 2020)Consejerio de Transformoción Económico,Industria,Conocimiento y Universidades,Junta de Andolucío,Espa?a",and grant No.A-CTS-498-UGR18by"Programa Operotivo FEDER Andalucía 2014-2020,Universidod de Granada,Junta de Andalucía,Espa?a",ca-funded by ERDF-FEDER,the European Union(all to VC)。
文摘Growth-associated protein 43 plays a key role in neurite outgrowth through cytoskeleton remodeling.We have previously demonstrated that structural damage of peripheral nerves induces growth-associated protein 43 upregulation to promote growth cone formation.Conversely,the limited regenerative capacity of the central nervous system due to an inhibitory environment prevents major changes in neurite outgrowth and should be presumably associated with low levels of growth-associated protein 43 expression.However,central alterations due to peripheral nerve damage have never been assessed using the growthassociated protein 43 marker.In this study,we used the tubulization technique to repair 1 cm-long nerve gaps in the rat nerve injury/repair model and detected growth-associated protein 43 expression in the peripheral and central nervous systems.First,histological analysis of the regeneration process confirmed an active regeneration process of the nerve gaps through the conduit from 10 days onwards.The growth-associated protein 43 expression profile varied across regions and follow-up times,from a localized expression to an abundant and consistent expression throughout the regeneration tissue,confirming the presence of an active nerve regeneration process.Second,spinal cord changes were also histologically assessed,and no apparent changes in the structural and cellular organization were observed using routine staining methods.Surprisingly,remarkable differences and local changes appeared in growth-associated protein 43 expression at the spinal cord level,in particular at 20 days post-repair and beyond.Growth-associated protein 43 protein was first localized in the gracile fasciculus and was homogeneously distributed in the left posterior cord.These findings differed from the growth-associated protein 43 pattern observed in the healthy control,which did not express growth-associated protein 43 at these levels.Our results revealed a differential expression in growth-associated protein 43 protein not only in the regenerating nerve tissue but also in the spinal cord after peripheral nerve transection.These findings open the possibility of using this marker to monitor changes in the central nervous system after peripheral nerve injury.
基金Supported by the CAPES/COFECUB,No.797-14the National Council for Research–Brazil,No.477915/2012-4.
文摘BACKGROUND Perinatal exposure to a poor nutritional environment predisposes the progeny to the development of metabolic disease at the adult age,both in experimental models and humans.Numerous adaptive responses to maternal protein restriction have been reported in metabolic tissues.However,the expression of glucose/fatty acid metabolism-related genes in adipose tissue and liver needs to be described.AIM To evaluate the metabolic impact of perinatal malnutrition,we determined malnutrition-associated gene expression alterations in liver and adipose tissue.METHODS In the present study,we evaluated the alterations in gene expression of glycolytic/Krebs cycle genes(Pyruvate dehydrogenase kinase 4 and citrate synthase),adipogenic and lipolytic genes and leptin in the adipose tissue of offspring rats at 30 d and 90 d of age exposed to maternal isocaloric low protein(LP)diet throughout gestation and lactation.We also evaluated,in the livers of the same animals,the same set of genes as well as the gene expression of the transcription factors peroxisome proliferator-activated receptor gamma coactivator 1,forkhead box protein O1 and hepatocyte nuclear factor 4 and of gluconeogenic genes.RESULTS In the adipose tissue,we observed a transitory(i.e.,at 30 d)downregulation of pyruvate dehydrogenase kinase 4,citrate synthase and carnitine palmitoyl transferase 1b gene expression.Such transcriptional changes did not persist in adult LP rats(90 d),but we observed a tendency towards a decreased gene expression of leptin(P=0.052).The liver featured some gene expression alterations comparable to the adipose tissue,such as pyruvate dehydrogenase kinase 4 downregulation at 30 d and displayed other tissue-specific changes,including citrate synthase and fatty acid synthase upregulation,but pyruvate kinase downregulation at 30 d in the LP group and carnitine palmitoyl transferase 1b downregulation at 90 d.These gene alterations,together with previously described changes in gene expression in skeletal muscle,may account for the metabolic adaptations in response to maternal LP diet and highlight the occurrence of persistent transcriptional defects in key metabolic genes that may contribute to the development of metabolic alterations during the adult life as a consequence of perinatal malnutrition.CONCLUSION We conclude that perinatal malnutrition relays long-lasting transcriptional alterations in metabolically active organs,i.e.,liver and adipose tissue.
基金supported by National Basic Research Program of China (2013CB127305, 2012CB124704)National Nature Science Foundation of China (31110103909, 31330075)+3 种基金Nature Science Foundation of Hunan (2015JJ2146)The Chinese Academy of Sciences STS Project(KFJ-EW-STS-063)Key Projects in the National Science & Technology Pillar Program (2013BAD21B04)Hunan Province project (2014GK1007)
文摘This experiment was conducted to investigate the effects of branched-chain amino acids(BCAA)supplemented in protein-restricted diets on the growth performance and the expression profile of amino acid transporters and energy metabolism related regulators in the white adipose tissue(WAT)of different regional depots including dorsal subcutaneous adipose(DSA) and abdominal subcutaneous adipose(ASA), A total of 24 crossbred barrows(7.40 ± 0.70 kg) were randomly divided into 4 groups and were fed the following isocaloric diets for 33 days: 1) a recommended adequate protein diet(AP, 20% CP, as a positive control); 2) a low protein diet(LP, 17% CP); 3) the LP diet supplemented with BCAA(LP + B, 17% CP) to reach the same level of the AP diet group; 4) the LP diet supplemented with 2 times the amount of BCAA(LP + 2B, 17% CP). The daily gain and daily feed intake of the LP diet group were the lowest among all the treatments(P < 0.01). The feed conversion was improved markedly in the group of LP + B compared with the LP diet group(P < 0.05). No significant difference was noted for the serum biochemical parameter concentrations of glucose, triglyceride, nonesterified fatty acid and insulin among the groups(P > 0.05). Moreover, BCAA supplementation down-regulated the expression levels of amino acid transporters including L-type amino acid transporter 1 and sodium-coupled neutral amino acid transporter 2 in DSA, but up-regulated the expression level of Ltype amino acid transporter 4 in ASA(P < 0.05), Meanwhile, the energy sensor AMP-activated protein kinase α was activated in the DSA of pigs fed LP diet and in the ASA of the pigs fed AP or LP + 2B diets(P < 0.05). The mRNA expression profile of the selected mitochondrial component and mitochondrial biogenesis associated regulators in DSA and ASA also responded differently to dietary BCAA supplementation. These results suggested that the growth performance of growing pigs fed protein restricted diets supplemented with BCAA could catch up to that of the pigs fed AP diets. The results also partly demonstrated that the regulation mechanisms of BCAA are different in the adipose tissues of different depots.
文摘Repetitive transcranial magnetic stimulation （rTMS） has been utilized as a therapeutic tool for neurodegenerative disorders including Alzheimer＇s disease. However, the precise mechanisms of its clinical effects remain unknown. β-amyloid （Aβ） exhibits direct neurotoxic effects and is closely related to neuronal degeneration in Alzheimer＇s disease. Therefore, it has been hypothesized that the neuroprotective effects of rTMS are related to the mechanisms of protection against Aβ neurotoxicity. Organotypic hippocampal slices were prepared from 8-day old, Sprague Dawley rats. The tissue slices were exposed to 100 μmol/L Al3142 since day 12 in vitro with and without high-frequency （20 Hz） magnetic stimulation. Magnetic stimulation efficacy was evaluated by measuring neuronal nuclei （NeuN） protein expression and by observing cultures following propidium iodide fluorescence staining and bromodeoxyuridine （BrdU） immunohistochemistry. Lactate dehydrogenase activity was detected in the culture media to evaluate hippocampal neuronal damage. Our results demonstrated that high-frequency magnetic stimulation significantly reversed the reduction of NeuN protein expression because of Aβ1-42 exposure （P 〈 0.05） and significantly reduced the number of damaged cells in the hippocampal slices （P 〈 0.05）. However, lactate dehydrogenase levels and anti-BrdU staining results did not reveal any statistical differences These findings indicate that high-frequency magnetic stimulation might have protective effect on hippocampal neurons from Aβ1-42 neurotoxicity.
