Background:The search for alternatives to antibiotics in pig production has increased the interest in natural resources with antimicrobial properties,such as medium-chain fatty acids(MCFA)as in-feed additives.This stu...Background:The search for alternatives to antibiotics in pig production has increased the interest in natural resources with antimicrobial properties,such as medium-chain fatty acids(MCFA)as in-feed additives.This study evaluated the potential of a novel blend of MCFA salts(DIC)from distilled coconut oil with a lauric acid content to reduce enteropathogens and control intestinal diseases around weaning.Two experimental disease models were implemented in early-weaned piglets,consisting of two oral challenges:Salmonella Typhimurium(1.2×10~8 CFU)or enterotoxigenic Escherichia coli(ETEC)F4(1.5×10~9 CFU).The parameters assessed were:animal performance,clinical signs,pathogen excretion,intestinal fermentation,immune-inflammatory response,and intestinal morphology.Results:The Salmonella challenge promoted an acute course of diarrhea,with most of the parameters responding to the challenge,whereas the ETEC F4 challenge promoted a mild clinical course.A consistent antipathogenic effect of DIC was observed in both trials in the hindgut,with reductions in Salmonella spp.plate counts in the cecum(P=0.03)on d 8 post-inoculation(PI)(Salmonella trial),and of enterobacteria and total coliform counts in the ileum and colon(P<0.10)on d 8 PI(ETEC F4 trial).When analyzing the entire colonic microbiota(16 S rRNA gene sequencing),this additive tended(P=0.13)to reduce the Firmicutes/Bacteroidetes ratio and enriched Fibrobacteres after the Salmonella challenge.In the ETEC F4 challenge,DIC prompted structural changes in the ecosystem with increases in Dialister,and a trend(P=0.14)to increase the Veillonellaceae family.Other parameters such as the intestinal fermentation products or serum pro-inflammatory mediators were not modified by DIC supplementation,nor were the histological parameters.Only the intraepithelial lymphocyte(IEL)counts were lowered by DIC in animals challenged with Salmonella(P=0.07).With ETEC F4,the IEL counts were higher with DIC on d 8 PI(P=0.08).Conclusions:This study confirms the potential activity of this MCFA salts mixture to reduce intestinal colonization by opportunistic pathogens such as Salmonella or E.coli and its ability to modulate colonic microbiota.These changes could explain to some extent the local immune cell response at the ileal level.展开更多
This research aims to identify the key fatty acid beta-oxidation(FAO)genes that are altered in kidney renal clear cell carcinoma(KIRC)and to analyze the role of these genes in KIRC The Gene Expression Omnibus(GEO)and ...This research aims to identify the key fatty acid beta-oxidation(FAO)genes that are altered in kidney renal clear cell carcinoma(KIRC)and to analyze the role of these genes in KIRC The Gene Expression Omnibus(GEO)and FAO datasets were used to identify these key genes.Wilcoxon rank sum test was used to assess the levels of acyl-CoA dehydrogenase medium chain(ACADM)between KIRC and non cancer samples.The logistic regression and Wilcoxon rank sum test were used to explore the association between ACADM and clinical features.The diagnostic performance of ACADM for KIRC was asessed using a diagnostic receiver operating ch aracteristic(ROC)curve.The co-expressed genes of ACADM were identifed in LinkedOmics database,and their function and pathway enrichment were analyzed.The correlation between ACADM expression level and immune infitration was analyzed by Gene Set Variation Analysis(GSVA)method Additionally,the proliferation,migration,and invasion abilities of KIRC cells were assessed after overexpressing ACADM.Following differential analysis and intersection,we identifed six hub genes,induding ACADM.We found that the expression level of ACADM was decreased in KIRC tissues and had a better diagnostic efect(AUC=0.916).Survival analysis suggested that patients with decreased ACADM expression had a worse prognosis.According to correlation analysis,a variety of dinical features were associated with the expression level of ACADML By analyzing the infiltration level of immune cells,we found that ACADM may be related to the enrichment of immune cells.Finally,ACADM overexpression inhibited proliferation,migration,and invasion of KIRC cells.In conclusion,our findings suggest that reduced ACADM expression in KIRC patients is indicative of poor prognosis.These results imply that ACADM may be a diagnostic and prognostic marker for individuals with KIRC,offering a reference for dinicians in diagnosis and treatment.展开更多
To investigate whether increasing tricarboxylic acid(TCA)cycle activity and ketogenic capacity would augment fatty acid(FA)oxidation induced by the peroxisome proliferator-activated receptor-alpha(PPARα)agonist clofi...To investigate whether increasing tricarboxylic acid(TCA)cycle activity and ketogenic capacity would augment fatty acid(FA)oxidation induced by the peroxisome proliferator-activated receptor-alpha(PPARα)agonist clofibrate,suckling newborn piglets(n=54)were assigned to 8 groups following a 2(±clofibrate)×4(glycerol succinate[SUC],triglycerides of 2-methylpentanoic acid[T2M],valeric acid[TC5]and hexanoic acid[TC6])factorial design.Each group was fed an isocaloric milk formula containing either 0%or 0.35%clofibrate(wt/wt,dry matter basis)with 5%SUC,T2M,TC5 or TC6 for 5 d.Another 6 pigs served as newborn controls.Fatty acid oxidation was examined in fresh homogenates of liver collected on d 6 using[1-^(14)C]palmitic acid(1 mM)as a substrate(0.265μCi/μmol).Measurements were performed in the absence or presence of L-carnitine(1 mM)or inhibitors of 3-hydroxy-3-methylglutaryl-CoA synthase(L659699,1.6μM)or acetoacetate-CoA deacylase(iodoacetamide,50μM).Without clofibrate stimulation,^(14)C accumulation in CO_(2) was higher from piglets fed diets containing T2M and TC5 than SUC,but similar to those fed TC6.Under clofibrate stimulation,accumulation also was higher in homogenates from piglets fed TC5 than all other dietary treatments.Interactions between clofibrate and carnitine or the inhibitors were observed(P=0.0004)for acid soluble products(ASP).In vitro addition of carnitine increased^(14)C-ASP(P<0.0001)above all other treatments,regardless of clofibrate treatment.The percentage of^(14)C in CO_(2) was higher(P=0.0023)in TC5 than in the control group.From these results we suggest that dietary supplementation of anaplerotic and ketogenic FA could impact FA oxidation and modify the metabolism of acetyl-CoA(product ofβ-oxidation)via alteration of TCA cycle activity,but the modification has no significant impact on the hepatic FA oxidative capacity induced by PPARα.In addition,the availability of carnitine is a critical element to maintain FA oxidation during the neonatal period.展开更多
n-Caproate,which is produced via chain elongation(CE)using waste biomass,can supply various fossilderived products,thus advancing the realization of carbon neutrality.Ammonia released from the degradation of nitrogen-...n-Caproate,which is produced via chain elongation(CE)using waste biomass,can supply various fossilderived products,thus advancing the realization of carbon neutrality.Ammonia released from the degradation of nitrogen-rich waste biomass can act as a nutrient or an inhibitor in anaerobic bioprocesses,including CE,with the distinction being primarily dependent on its concentration.Currently,the optimal concentration of ammonia and the threshold of toxicity for open-culture n-caproate production using ethanol as an electron donor,along with the underlying mechanisms,remain unclear.This study revealed that the optimal concentration of ammonia for n-caproate production was 2.0 g∙L^(-1),whereas concentrations exceeding this threshold markedly suppressed the CE performance.Exploration of the mechanism revealed the involvement of two forms of ammonia(i.e.,ammonium ions and free ammonia)in this inhibitory behavior.High ammonia levels(5.0 g∙L^(-1))induced excessive ethanol oxidation and suppressed the reverse β-oxidation(RBO)process,directly leading to the enhanced activities of enzymes(phosphotransacetylase and acetate kinase)responsible for acetate formation and diminished activities of butyryl-coenzyme A(CoA):acetyl-CoA transferase,caproyl-CoA:butyryl-CoA transferase,and caproyl-CoA:acetyl-CoA transferase that are involved in the syntheses of n-butyrate and n-caproate.Furthermore,the composition of the microbial community shifted from Paraclostridium dominance(at 0.1 g∙L^(-1)ammonia)to a co-dominance of Fermentimonas,Clostridium sensu stricto 12,and Clostridium sensu stricto 15 at 2.0 g∙L^(-1)ammonia.However,these CE-functional bacteria were mostly absent in the presence of excessive ammonia(5.0 g∙L^(-1)ammonia).Metagenomic analysis revealed the upregulation of functions such as RBO,fatty acid synthesis,K^(+)efflux,adenosine triphosphatase(ATPase)metabolism,and metal cation export in the presence of 2.0 g∙L^(-1)ammonia,collectively contributing to enhanced n-caproate production.Conversely,the aforementioned functions(excluding metal cation export)and K^(+)influx were suppressed by excessive ammonia,undermining both ammonia detoxification and n-caproate biosynthesis.The comprehensive elucidation of ammonia-driven mechanisms influencing n-caproate production,as provided in this study,is expected to inspire researchers to devise effective strategies to alleviate ammonia-induced inhibition.展开更多
Carnitine Palmitoyl Transferase II (CPTII) is a very important enzyme that helps with the oxidation of long-chain fatty acid to produce energy. Deficiency in CPTII will lead to energy deficiency in the case of fasting...Carnitine Palmitoyl Transferase II (CPTII) is a very important enzyme that helps with the oxidation of long-chain fatty acid to produce energy. Deficiency in CPTII will lead to energy deficiency in the case of fasting and the accumulation of the long chain fatty in the body. There are three types of CPT II deficiency, the myopathic form, the severe infantile hepatocardiomuscular form and the lethal neonatal form. They are all inherited as an autosomal recessive. Diagnosis of the CPTII are 1) tandem mass spectrometry (MS/MS) in adult form and 2) CPTII polymorphism (F352C), which is linked to reducing the activity of CPTII in infantile form [1]. Glucose is the primary management and medium-chain fatty acid is an alternative due to the bypass of the CPTII enzyme in the pathway. For the prevention of CPTII deficiency are to avoid long chain fatty acid (C12-fatty acid), fasting, prolonged exercise, known triggers, and certain medications such as anti-epileptics and general anesthesia. During the rhabdomyolysis and myoglobinuria attack, it is very important to maintain hydration to avoid acute renal failure. If, however, renal failure occurs, dialysis is recommended. We present a case of a 27-year-old African American woman with the significant past medical history of CPT II deficiency leading to recurrent rhabdomyolysis and myoglobinuria. Together with all the research studies from diagnosis to treatment of CPTII deficiency will help in clinical management of patients. And this case report will add to the existing case reports of patients who have CPTII deficiency in terms of how we diagnose, how we treat, and how we prevent symptoms from re-occurring.展开更多
基金funded by the“PORCDIGEST”project(IDI-20140262)funded by the CDTI and the Ministerio de Economía y Competitividad(Spain)support from the pre-doctoral FI grant of the Generalitat de Catalunya(Spain)awarded to Paola López-Colom.
文摘Background:The search for alternatives to antibiotics in pig production has increased the interest in natural resources with antimicrobial properties,such as medium-chain fatty acids(MCFA)as in-feed additives.This study evaluated the potential of a novel blend of MCFA salts(DIC)from distilled coconut oil with a lauric acid content to reduce enteropathogens and control intestinal diseases around weaning.Two experimental disease models were implemented in early-weaned piglets,consisting of two oral challenges:Salmonella Typhimurium(1.2×10~8 CFU)or enterotoxigenic Escherichia coli(ETEC)F4(1.5×10~9 CFU).The parameters assessed were:animal performance,clinical signs,pathogen excretion,intestinal fermentation,immune-inflammatory response,and intestinal morphology.Results:The Salmonella challenge promoted an acute course of diarrhea,with most of the parameters responding to the challenge,whereas the ETEC F4 challenge promoted a mild clinical course.A consistent antipathogenic effect of DIC was observed in both trials in the hindgut,with reductions in Salmonella spp.plate counts in the cecum(P=0.03)on d 8 post-inoculation(PI)(Salmonella trial),and of enterobacteria and total coliform counts in the ileum and colon(P<0.10)on d 8 PI(ETEC F4 trial).When analyzing the entire colonic microbiota(16 S rRNA gene sequencing),this additive tended(P=0.13)to reduce the Firmicutes/Bacteroidetes ratio and enriched Fibrobacteres after the Salmonella challenge.In the ETEC F4 challenge,DIC prompted structural changes in the ecosystem with increases in Dialister,and a trend(P=0.14)to increase the Veillonellaceae family.Other parameters such as the intestinal fermentation products or serum pro-inflammatory mediators were not modified by DIC supplementation,nor were the histological parameters.Only the intraepithelial lymphocyte(IEL)counts were lowered by DIC in animals challenged with Salmonella(P=0.07).With ETEC F4,the IEL counts were higher with DIC on d 8 PI(P=0.08).Conclusions:This study confirms the potential activity of this MCFA salts mixture to reduce intestinal colonization by opportunistic pathogens such as Salmonella or E.coli and its ability to modulate colonic microbiota.These changes could explain to some extent the local immune cell response at the ileal level.
基金the National Natural Science Foundation of China(Grant Nos.82072816 and 81672553)the Natural Science Foundation of Shandong Province(Grant No.ZR2021LZY003).
文摘This research aims to identify the key fatty acid beta-oxidation(FAO)genes that are altered in kidney renal clear cell carcinoma(KIRC)and to analyze the role of these genes in KIRC The Gene Expression Omnibus(GEO)and FAO datasets were used to identify these key genes.Wilcoxon rank sum test was used to assess the levels of acyl-CoA dehydrogenase medium chain(ACADM)between KIRC and non cancer samples.The logistic regression and Wilcoxon rank sum test were used to explore the association between ACADM and clinical features.The diagnostic performance of ACADM for KIRC was asessed using a diagnostic receiver operating ch aracteristic(ROC)curve.The co-expressed genes of ACADM were identifed in LinkedOmics database,and their function and pathway enrichment were analyzed.The correlation between ACADM expression level and immune infitration was analyzed by Gene Set Variation Analysis(GSVA)method Additionally,the proliferation,migration,and invasion abilities of KIRC cells were assessed after overexpressing ACADM.Following differential analysis and intersection,we identifed six hub genes,induding ACADM.We found that the expression level of ACADM was decreased in KIRC tissues and had a better diagnostic efect(AUC=0.916).Survival analysis suggested that patients with decreased ACADM expression had a worse prognosis.According to correlation analysis,a variety of dinical features were associated with the expression level of ACADML By analyzing the infiltration level of immune cells,we found that ACADM may be related to the enrichment of immune cells.Finally,ACADM overexpression inhibited proliferation,migration,and invasion of KIRC cells.In conclusion,our findings suggest that reduced ACADM expression in KIRC patients is indicative of poor prognosis.These results imply that ACADM may be a diagnostic and prognostic marker for individuals with KIRC,offering a reference for dinicians in diagnosis and treatment.
基金This work is supported by Animal Nutrition,Growth and Lactation(grant no.2015-67015-23245/project accession no.1005855)from the USDA National Institute of Food and Agriculturethe North Carolina Agricultural Research Hatch projects 1016618 and 02780。
文摘To investigate whether increasing tricarboxylic acid(TCA)cycle activity and ketogenic capacity would augment fatty acid(FA)oxidation induced by the peroxisome proliferator-activated receptor-alpha(PPARα)agonist clofibrate,suckling newborn piglets(n=54)were assigned to 8 groups following a 2(±clofibrate)×4(glycerol succinate[SUC],triglycerides of 2-methylpentanoic acid[T2M],valeric acid[TC5]and hexanoic acid[TC6])factorial design.Each group was fed an isocaloric milk formula containing either 0%or 0.35%clofibrate(wt/wt,dry matter basis)with 5%SUC,T2M,TC5 or TC6 for 5 d.Another 6 pigs served as newborn controls.Fatty acid oxidation was examined in fresh homogenates of liver collected on d 6 using[1-^(14)C]palmitic acid(1 mM)as a substrate(0.265μCi/μmol).Measurements were performed in the absence or presence of L-carnitine(1 mM)or inhibitors of 3-hydroxy-3-methylglutaryl-CoA synthase(L659699,1.6μM)or acetoacetate-CoA deacylase(iodoacetamide,50μM).Without clofibrate stimulation,^(14)C accumulation in CO_(2) was higher from piglets fed diets containing T2M and TC5 than SUC,but similar to those fed TC6.Under clofibrate stimulation,accumulation also was higher in homogenates from piglets fed TC5 than all other dietary treatments.Interactions between clofibrate and carnitine or the inhibitors were observed(P=0.0004)for acid soluble products(ASP).In vitro addition of carnitine increased^(14)C-ASP(P<0.0001)above all other treatments,regardless of clofibrate treatment.The percentage of^(14)C in CO_(2) was higher(P=0.0023)in TC5 than in the control group.From these results we suggest that dietary supplementation of anaplerotic and ketogenic FA could impact FA oxidation and modify the metabolism of acetyl-CoA(product ofβ-oxidation)via alteration of TCA cycle activity,but the modification has no significant impact on the hepatic FA oxidative capacity induced by PPARα.In addition,the availability of carnitine is a critical element to maintain FA oxidation during the neonatal period.
基金supported by the Natural Science Foundation of Sichuan Province(2022NSFSC1042)the National Natural Science Foundation of China(52000132)the Open Project of the State Key Laboratory of Urban Water Resource and Environment(HC202241).
文摘n-Caproate,which is produced via chain elongation(CE)using waste biomass,can supply various fossilderived products,thus advancing the realization of carbon neutrality.Ammonia released from the degradation of nitrogen-rich waste biomass can act as a nutrient or an inhibitor in anaerobic bioprocesses,including CE,with the distinction being primarily dependent on its concentration.Currently,the optimal concentration of ammonia and the threshold of toxicity for open-culture n-caproate production using ethanol as an electron donor,along with the underlying mechanisms,remain unclear.This study revealed that the optimal concentration of ammonia for n-caproate production was 2.0 g∙L^(-1),whereas concentrations exceeding this threshold markedly suppressed the CE performance.Exploration of the mechanism revealed the involvement of two forms of ammonia(i.e.,ammonium ions and free ammonia)in this inhibitory behavior.High ammonia levels(5.0 g∙L^(-1))induced excessive ethanol oxidation and suppressed the reverse β-oxidation(RBO)process,directly leading to the enhanced activities of enzymes(phosphotransacetylase and acetate kinase)responsible for acetate formation and diminished activities of butyryl-coenzyme A(CoA):acetyl-CoA transferase,caproyl-CoA:butyryl-CoA transferase,and caproyl-CoA:acetyl-CoA transferase that are involved in the syntheses of n-butyrate and n-caproate.Furthermore,the composition of the microbial community shifted from Paraclostridium dominance(at 0.1 g∙L^(-1)ammonia)to a co-dominance of Fermentimonas,Clostridium sensu stricto 12,and Clostridium sensu stricto 15 at 2.0 g∙L^(-1)ammonia.However,these CE-functional bacteria were mostly absent in the presence of excessive ammonia(5.0 g∙L^(-1)ammonia).Metagenomic analysis revealed the upregulation of functions such as RBO,fatty acid synthesis,K^(+)efflux,adenosine triphosphatase(ATPase)metabolism,and metal cation export in the presence of 2.0 g∙L^(-1)ammonia,collectively contributing to enhanced n-caproate production.Conversely,the aforementioned functions(excluding metal cation export)and K^(+)influx were suppressed by excessive ammonia,undermining both ammonia detoxification and n-caproate biosynthesis.The comprehensive elucidation of ammonia-driven mechanisms influencing n-caproate production,as provided in this study,is expected to inspire researchers to devise effective strategies to alleviate ammonia-induced inhibition.
文摘Carnitine Palmitoyl Transferase II (CPTII) is a very important enzyme that helps with the oxidation of long-chain fatty acid to produce energy. Deficiency in CPTII will lead to energy deficiency in the case of fasting and the accumulation of the long chain fatty in the body. There are three types of CPT II deficiency, the myopathic form, the severe infantile hepatocardiomuscular form and the lethal neonatal form. They are all inherited as an autosomal recessive. Diagnosis of the CPTII are 1) tandem mass spectrometry (MS/MS) in adult form and 2) CPTII polymorphism (F352C), which is linked to reducing the activity of CPTII in infantile form [1]. Glucose is the primary management and medium-chain fatty acid is an alternative due to the bypass of the CPTII enzyme in the pathway. For the prevention of CPTII deficiency are to avoid long chain fatty acid (C12-fatty acid), fasting, prolonged exercise, known triggers, and certain medications such as anti-epileptics and general anesthesia. During the rhabdomyolysis and myoglobinuria attack, it is very important to maintain hydration to avoid acute renal failure. If, however, renal failure occurs, dialysis is recommended. We present a case of a 27-year-old African American woman with the significant past medical history of CPT II deficiency leading to recurrent rhabdomyolysis and myoglobinuria. Together with all the research studies from diagnosis to treatment of CPTII deficiency will help in clinical management of patients. And this case report will add to the existing case reports of patients who have CPTII deficiency in terms of how we diagnose, how we treat, and how we prevent symptoms from re-occurring.