A morphologically structured model is proposed to describe the batch fermentation of lovastatin according to the growth kinetics of filamentous microorganisms. Three kinds of hyphae are considered in the model: active...A morphologically structured model is proposed to describe the batch fermentation of lovastatin according to the growth kinetics of filamentous microorganisms. Three kinds of hyphae are considered in the model: actively growing hyphae, non-growing hyphae and deactivated hyphae. Furthermore, actively growing hyphae consist of three morphological compartments: apical compartment which gives rise to hyphal tip extension; subapical compartment which is related to hyphal branching; and hyphal compartment which is only responsible for secondary metabolite formation. The kinetics of mycelial growth mechanism is summarized and applied in modeling lovastatin fermentation. A Michaelis-Menten kinetic model with substrate inhibition is proposed for product formation. As expected, the model simulations fit well with experimental data obtained either from a laboratory scale 10L fer-menter or from a pilot-plant scale fermenter.展开更多
Two metabolites (A and B) were isolated from the mycelium of mangrove endophytic fungus Stysanus like sp. (#2492) from the South China Sea. Their structures were identified by spectral data as N-(2-hydroxytetraco...Two metabolites (A and B) were isolated from the mycelium of mangrove endophytic fungus Stysanus like sp. (#2492) from the South China Sea. Their structures were identified by spectral data as N-(2-hydroxytetracosyl)-2-amino-1,3,4-trihydroxyoctadecane (A) and γ -stearolactone (B). It is the first report that γ -stearolactone (B) is isolated from marine fungus as natural product.展开更多
Twenty patients with diabetes type-2, aged between 38 and 61 years, with at least one cardiovascular risk factor were divided in two groups (Group-1 included newly diagnosed type 2 diabetic patients without treatment...Twenty patients with diabetes type-2, aged between 38 and 61 years, with at least one cardiovascular risk factor were divided in two groups (Group-1 included newly diagnosed type 2 diabetic patients without treatment with oral antidiabetic OAD, Group-2: patients with diabetes type 2 under OAD +/- insulin (N = 11)). Patients from both groupswere taking Nicotinamide Adenine Dinucleotide (NADH) Rapid Energy 80 mg/day in two takes for a period of 56 days. A greater reduction in average fasting glucose and HbAlc after 56 days was observed in the patients of group 1 not taking metformin compared to patients of group-2 which were taking metformin. Why metformin reduces the anti-diabetic effect of NADH will be discussed.展开更多
Effects of two doses of the anti-diabetic drug, metformin (MF), on hormonal and metabolic levels of serum of non-diabetic male Wistar rats with 1,2-dimethylhydrazine (DMH)-induced colon tumor adenocarcinomas were ...Effects of two doses of the anti-diabetic drug, metformin (MF), on hormonal and metabolic levels of serum of non-diabetic male Wistar rats with 1,2-dimethylhydrazine (DMH)-induced colon tumor adenocarcinomas were studied. Carcinogenesis in the animals was also observed. Rats with DMH-induced colon adenocarcinomas had elevated levels of serum glucose, insulin, insulin- like growth factor-l, total cholesterol, triglycerides, catalase, malonic dialdehyde, glycated hemoglobin, aspartate aminotransferase, and alanine aminotransferase and decreased hemoglobin. Treatment with two doses of MF normalized maiority of these changes in DMH-treated rats, whereas the drug was ineffective in rats without DMH treatment. The only exception was the decreased triglyceride levels in MF-treated rats. A 100 mg/kg dose of MF increased DMH-induced exophytic colon carcinomas and decreased endophytic tumors compared with untreated rats. Moreover, both MF doses increased DMH-induced and highly differentiated tumors and decreased the invasiveness of colon carcinomas compared with rats provided with DMH and water. Therefore, effects of MF on metabolic homeostasis are critical for preventing colon cancer.展开更多
In order to overcome the elementary heterogeneous nucleation whileoctahydro trisodium salt of fructose- 1, 6-diphosphate (FDPNa_3·8H_2O) is crystallized with ethanol precipitation at low temperature,a new crystal...In order to overcome the elementary heterogeneous nucleation whileoctahydro trisodium salt of fructose- 1, 6-diphosphate (FDPNa_3·8H_2O) is crystallized with ethanol precipitation at low temperature,a new crystallization method with alcohol precipitation combined withsalt precipitation has been presented. The ethanol-sodium ac- etatesystem for crystallization of salt of fructose-1, 6-diphosphate isbased on the mechanism of crystallization of FDPNA_3·8H_2O in theethanol-low temperature system. It is found that crystal size may becontrolled by regulating Temperature of pH value of solution in thecrystallization process, and the crystal yield increases to 95/100from 78/100 Which obtained in the ethanol-low temperature system.展开更多
AIM: To study the metabolic profiling of serum samples from compensated and decompensated cirrhosis patients. METHODS: A pilot metabolic profiling study was conducted using three groups: compensated cirrhosis patients...AIM: To study the metabolic profiling of serum samples from compensated and decompensated cirrhosis patients. METHODS: A pilot metabolic profiling study was conducted using three groups: compensated cirrhosis patients (n = 30), decompensated cirrhosis patients (n = 30) and healthy controls (n = 30). A 1H nuclear magnetic resonance (NMR)-based metabonomics approach was used to obtain the serum metabolic profiles of the samples. The acquired data were processed by multivariate principal component analysis and orthogonal partial least-squares discriminant analysis (OPLS-DA). RESULTS: The OPLS-DA model was capable of distinguishing between decompensated and compensated cirrhosis patients, with an R2Y of 0.784 and a Q2Y of 0.598. Twelve metabolites, such as pyruvate, phenylala-nine and succinate, were identified as the most influential factors for the difference between the two groups. The validation of the diagnosis prediction showed that the accuracy of the OPLS-DA model was 85% (17/20). CONCLUSION: 1H NMR spectra combined with pattern recognition analysis techniques offer a new way to diagnose compensated and decompensated cirrhosis in the future.展开更多
Alcoholism is a major health problem in the United States and worldwide,and alcohol remains the single most significant cause of liver-related diseases and deaths.Alcohol is known to influence nutritional status at ma...Alcoholism is a major health problem in the United States and worldwide,and alcohol remains the single most significant cause of liver-related diseases and deaths.Alcohol is known to influence nutritional status at many levels including nutrient intake,absorption,utilization,and excretion,and can lead to many nutritional disturbances and deficiencies.Nutrients can dramatically affect gene expression and alcohol-induced nutrient imbalance may be a major contributor to pathogenic gene expression in alcohol-induced liver disease(ALD).There is growing interest regarding epigenetic changes,including histone modifications that regulate gene expression during disease pathogenesis.Notably,modifications of core histones in the nucleosome regulate chromatin structure and DNA methylation,and control gene transcription.This review highlights the role of nutrient disturbances brought about during alcohol metabolism and their impact on epigenetic histone modifications that may contribute to ALD.The review is focused on four critical metabolites,namely,acetate,S-adenosylmethionine,nicotinamide adenine dinucleotide and zinc that are particularly relevant to alcohol metabolism and ALD.展开更多
Biodesulfurization (BDS) is a promising technology for deep desulfurization. In this work, Pseudomonas delafieldii R-8 cells are immobilized in calcium alginate beads and used for BDS of transportation fuels. It is ...Biodesulfurization (BDS) is a promising technology for deep desulfurization. In this work, Pseudomonas delafieldii R-8 cells are immobilized in calcium alginate beads and used for BDS of transportation fuels. It is found that thiophene and dibenzothiophene (DBT) can be simultaneously metabolized by immobilized R-8 cells. The initial sulfur content in the model oil is 300 mg·kg-1 (thiophene " DI3T= 1 " 1). After 10 h of treatment, the thiophene concentration is reduced by 40%, while DBT is reduced by 25%. The utilization rate of thiophene is faster than that of DBT. Moreover, the oil/water ratio of alginate immobilized cells is studied to reduce the water volume in desulfurization systems. Long-term recycling of BDS by alginate immobilized cells is carried out with oil/water ratio at 5 : 1. The immobilized cells are successfully reused over 15 batch cycles. In the last batch, the desulfurization activity remains at least 75% of the first batch.展开更多
Escherichia coli BW25113 was metabolically engineered for CoQ10 production by replacing ispB with ddsA from Gluconobacter suboxydans.Effects of precursor balance and reduced nicotinamide-adenine dinucleotide phosphate...Escherichia coli BW25113 was metabolically engineered for CoQ10 production by replacing ispB with ddsA from Gluconobacter suboxydans.Effects of precursor balance and reduced nicotinamide-adenine dinucleotide phosphate (NADPH) availability on CoQ10 production in E.coli were investigated.The knockout of pykFA along with pck overexpression could maintain a balance between glyceraldehyde 3-phosphate and pyruvate,increasing CoQ10 production.Replacement of native NAD-dependent gapA with NADP-dependent gapC from Clostridium acetobutylicum,together with the overexpression of gapC,could increase NADPH availability and then enhanced CoQ10 production.Three effects,overexpressions of various genes in CoQ biosynthesis and central metabolism,different vectors and culture conditions on CoQ10 production in E.coli,were all investigated.The investigation of different vectors indicated that low copy number vector may be more beneficial for CoQ10 production in E.coli.The recombinant E.coli (△ispB::ddsA,△pykFA and △gapA::gapC),harboring the two plasmids encoding pck,dxs,idi and ubiCA genes under the control of PT5 on pQE30,ispA,ddsA from Gluconobacter suboxydans and gapC from Clostridium acetobutylicum under the control of PBAD on pBAD33,could produce CoQ10 up to 3.24 mg·g-1 dry cell mass simply by changing medium from M9YG to SOB with phosphate salt and initial culture pH from 7.0 to 5.5.The yield is unprecedented and 1.33 times of the highest production so far in E.coli.展开更多
Exercise affects muscle metabolism and composition in the untrained muscles. The proteome of muscle tissue will be affected by exercise and resting. This is of economic importance for pork quality where transportation...Exercise affects muscle metabolism and composition in the untrained muscles. The proteome of muscle tissue will be affected by exercise and resting. This is of economic importance for pork quality where transportation relates to exercise of untrained muscles. Rest reverses exercise effects. The objective of this research was to develop potential protein biomarkers that predict the optimal resting time after exercise related to optimal pork quality. Ten litters of four female pigs were within litter allocated to the four treatment groups: exercise by running on a treadmill for 27 minutes followed by rest for 0, 1, or 3 h; control pigs without exercise. Proteome profiles and biochemical traits measuring energy metabolism and meat quality traits expected to be related to exercise were determined in the Longissimus and the Biceps femoris of the pigs. The results indicated associations between protein abundances in muscles and exercise, resting, and biochemical traits.展开更多
The fructose modified chitosan microcarries (CMs) were prepared by the reaction of glutaraldehyde with fructose-modified chitosan. Various factors that influence the preparation were studied and the reaction condition...The fructose modified chitosan microcarries (CMs) were prepared by the reaction of glutaraldehyde with fructose-modified chitosan. Various factors that influence the preparation were studied and the reaction conditions were optimized. Morphology of rat hepatocytes cultured on CMs was observed using phase contrast microscope and scanning electron microscope, and the metabolic activities were measured. Rat hepatocytes cultured on CMs retained the spherical shape as they have in vivo and had high metabolic activities. Fructose can enhance the metabolic activity of hepatocytes and the modified CMs are promising scaffold for hepatocytes attachment.展开更多
Statistical classification methods are frequently applied to analyze metabolomics data, especially from medicinal plants. Combined with variable selection techniques, we are able to identify marker candidates, which c...Statistical classification methods are frequently applied to analyze metabolomics data, especially from medicinal plants. Combined with variable selection techniques, we are able to identify marker candidates, which can be used to discriminate the group to which unknown subjects belong. After preprocessing, such as outlier checking, normalization, missing value imputation and transformation, we then mainly utilized four novel classification methods: RF (random forest), NSC (nearest shrunken centroid), PLS-DA (partial least square discriminant analysis) and SAM (significant analysis ofmicroarrays). Each method has its own device to measure the importance of single metabolite, so that, it is probable to choose highly ranked metabolites, which show the best prediction accuracy. Adapting above strategy, we have successfully analyzed several kinds of metabolomics data including Panax ginseng, Lespedeza species, Anemarrhean asphodeloides and Gastrodia elata.展开更多
Objective: The elevated incidence of obesity has been paralleled with higher risks of breast cancer. High adiposity increases leptin secretion from adipose tissue, which in turn increases cancer cell proliferation. Th...Objective: The elevated incidence of obesity has been paralleled with higher risks of breast cancer. High adiposity increases leptin secretion from adipose tissue, which in turn increases cancer cell proliferation. The interplay between leptin and estrogen is one of the mechanisms through which leptin influences breast carcinogenesis. An unbalanced estrogen metabolism increases the formations of catechol estrogen quinones, DNA adducts, and cancer mutations. This study aims to investigate the effect of leptin on some estrogen metabolic enzymes and DNA adduction in breast cancer cells.Methods: High performance liquid chromatography(HPLC) was performed to analyze the DNA adducts 4-OHE1[E2]-1-N3 adenine and 4-OHE1[E2]-1-N7 guanine. Reporter gene assay, real time reverse transcription polymerase chain reaction(real time RT-PCR), and Western blot were used to assess the expression of estrogen metabolizing genes and enzymes: Cytochrome P-4501B1(CYP1B1), Nicotinamide adenine dinucleotide phosphate-quinone oxidoreductase1(NQO1), and Catechol-O-methyl transferase(COMT).Results: Leptin significantly increased the DNA adducts 4-OHE1[E2]-1-N3 adenine and 4-OHE1[E2]-1-N7 guanine.Furthermore, leptin significantly upregulated CYP1B1 promoter activity and protein expression. The luciferase promoter activities of NQO1 and m RNA levels were significantly reduced. Moreover, leptin greatly reduced the reporter activities of the COMT-P1 and COMT-P2 promoters and diminished the protein expression of COMT.Conclusions: Leptin increases DNA adduct levels in breast cancer cells partly by affecting key genes and enzymes involved in estrogen metabolism. Thus, increased focus should be directed toward leptin and its effects on the estrogen metabolic pathway as an effective approach against breast cancer.展开更多
Mitochondria are increasingly recognized as important targets for tumor treatment because of their central roles in apoptotic pathways and cellular metabolism. Dichloroacetate (DCA), a low molecular weight mitochond...Mitochondria are increasingly recognized as important targets for tumor treatment because of their central roles in apoptotic pathways and cellular metabolism. Dichloroacetate (DCA), a low molecular weight mitochondria-targeting agent, exhibits potential therapeutic effects for tumors. Based on the effects of DCA on tumor cellular metabolism, we carried out this study to investigate the anti-tumor activity of DCA in C6 glioma cells in vitro. The results showed that DCA was able to increase the activity of pyruvate dehydrogenase (PDH), induce the production of reactive oxygen species (ROS) and reduce the mitochondrial membrane potential (MMP) in C6 ceils in vitro (P〈0.05 or 0.01), indicating that the anti-tumor effects of DCA in C6 cells could be through the activation of the mitochondrial pathway. In conclusion, mitochondria could be a viable therapeutic target for the treatment of glioma.展开更多
The effects of carbon (C) and nitrogen (N) sources on N utilization and biosynthesis of amino acids were examined in the germinating spores of the arbuscular mycorrhizal (AM) fungus Glomus intraradices Schenck ...The effects of carbon (C) and nitrogen (N) sources on N utilization and biosynthesis of amino acids were examined in the germinating spores of the arbuscular mycorrhizal (AM) fungus Glomus intraradices Schenck & Smith after exposure to various N substrates, CO2, glucose, and/or root exudates. The N uptake and de novo biosynthesis of amino acids were analyzed using stable isotopic labeling with mass spectrometric detection. High-performance liquid chromatography-based analysis was used to measure amino acid levels. In the absence of exogenous N sources and in the presence of 25 mL L^-1 CO2, the germinating AM fungal spores utilized internal N storage as well as C skeletons derived from the degradation of storage lipids to biosynthesize the free amino acids, in which serine and glycine were produced predominantly. The concentrations of internal amino acids increased gradually as the germination time increased from 0 to 1 or 2 weeks. However, asparagine and glutamine declined to the low levels; both degraded to provide the biosynthesis of other amino acids with C and N donors. The availability of exogenous inorganic N (ammonium and nitrate) and organic N (urea, arginine, and glutamine) to the AM fungal spores using only CO2 for germination generated more than 5 times more internal free amino acids than those in the absence of exogenous N. A supply of exogenous nitrate to the AM fungal spores with only CO2 gave rise to more than 10 times more asparagine than that without exogenous N. In contrast, the extra supply of exogenous glucose to the AM fungal spores generated a significant enhancement in the uptake of exogenous N sources, with more than 3 times more free amino acids being produced than those supplied with only exogenous CO2. Meanwhile, arginine was the most abundant free amino acid produced and it was incorporated into the proteins of AM funsal spores to serve as an N storage compound.展开更多
Good quality deoxyribonucleic acid (DNA) is the pre-requisite for its downstream applications. The presence of high concentrations of polysaccharides, polyphenols, proteins, and other secondary metabolites in mango ...Good quality deoxyribonucleic acid (DNA) is the pre-requisite for its downstream applications. The presence of high concentrations of polysaccharides, polyphenols, proteins, and other secondary metabolites in mango leaves poses problem in getting good quality DNA fit for polymerase chain reaction (PCR) applications. The problem is exacerbated when DNA is extracted from mature mango leaves. A reliable and modified protocol based on the cetyl trimethylammonium bromide (CTAB) method for DNA extraction from mature mango leaves is described here. High concentrations of inert salt were used to remove polysaccharides; Polyvinylpyrrolidone (PVP) and 13-mercaptoethanol were employed to man'age phenolic compounds. Extended chloroform-isoamyl alcohol treatment followed by RNase treatment yielded 950-1050 pg of good quality DNA, free of protein and RNA. The problems of DNA degradation,contamination, and low yield due to irreversible binding of phenolic compounds and coprecipitation of polysaccharides with DNA were avoided by this method, The DNA isolated by the modified method showed good PCR amplification using simple sequence repeat (SSR) primers, This modified protocol can also be used to extract DNA from other woody plants having similar problems.展开更多
Objective: To observe the influence of transcutaneous CO2 emission (TCE) at points on the meridian or beside the meridian after different stimulations like acupuncture De-qi, sham acupuncture, study the correlation...Objective: To observe the influence of transcutaneous CO2 emission (TCE) at points on the meridian or beside the meridian after different stimulations like acupuncture De-qi, sham acupuncture, study the correlation between acupuncture De-qi and local energy metabolism through TCE. Methods: Twenty healthy volunteers (male 8, female 12, average age 29 years old) were selected. Before, during and after five different acupuncture Neiguan (PC 6), the TCE was measured at Quze (PC 3), point A [at the lower one fourth of line between Tianquan (PC 2) and Quze (PC 3)] , point B [at the middle of line between Ximen (PC 4) and Quze (PC 3)], point C (2 cm ulnar side point A) and point D (2 cm ulnar side point B) with a high sensitive CO2 instrument (Frewil-Q.F., made in China). The measure results were compared. Results: The comparison on value of TCE before and after the acupuncture, in Sham acupuncture and shallow acupuncture groups, it increased in all five points; in De-qi acupuncture group, there are significant increase on point A, point B, and Quze (PC 3), it has statistic significance, but there are no significant increase on point C and D. After Ximen (PC 4) or Daling (PC 7) were pressed to block Neiguan (PC 6), the value of TCE on Quze (PC 3), point A and point B were decreased during acupuncture Neignan (PC 6), and increased after the block was removed, but there was no significant difference. Conclusion: Sham acupuncture has also some effects on body, it can increase energy metabolism of local skin, it may be the reason that shallow acupuncture without qi arriving can obtain clinical efficacy. The operation method of traditional qi arriving acupuncture can increase energy metabolism of relevant meridian skin, mechanical press can reduce this effect.展开更多
The peroxisome proliferator-activated receptors (PPARs), PPARt,, PPARβ/δ and PPARy, are ligand-activated transcriptional factors, which belong to the nuclear receptor super family and play crucial roles in glucose...The peroxisome proliferator-activated receptors (PPARs), PPARt,, PPARβ/δ and PPARy, are ligand-activated transcriptional factors, which belong to the nuclear receptor super family and play crucial roles in glucose and lipid metabolism. Based on the impressive advantages ofPPAR agonists (like TZD and fibrate compounds) in the treatment of metabolic syndrome and type 2 diebetes, PPAR modulators have doubtlessly grabbed much more attention. However, serious clinical adverse effects, especially for PPARy agonists, hinder the development of PPAR agonist, Therefore, the selectivity and safety would be the key points and have been taken into the consideration for novel generation PPAR agonist research, and then several dual- or pan-PPAR modulators have emerged. Furthermore, experimental study indicates that partial agonists can neutralize the side effect and achieve modest therapeutic effect. This review summaries structural features of PPAR receptors, illustrates the method of PPAR modulator design, then lists and analyzes recent dual- and nan- agonists展开更多
文摘A morphologically structured model is proposed to describe the batch fermentation of lovastatin according to the growth kinetics of filamentous microorganisms. Three kinds of hyphae are considered in the model: actively growing hyphae, non-growing hyphae and deactivated hyphae. Furthermore, actively growing hyphae consist of three morphological compartments: apical compartment which gives rise to hyphal tip extension; subapical compartment which is related to hyphal branching; and hyphal compartment which is only responsible for secondary metabolite formation. The kinetics of mycelial growth mechanism is summarized and applied in modeling lovastatin fermentation. A Michaelis-Menten kinetic model with substrate inhibition is proposed for product formation. As expected, the model simulations fit well with experimental data obtained either from a laboratory scale 10L fer-menter or from a pilot-plant scale fermenter.
文摘Two metabolites (A and B) were isolated from the mycelium of mangrove endophytic fungus Stysanus like sp. (#2492) from the South China Sea. Their structures were identified by spectral data as N-(2-hydroxytetracosyl)-2-amino-1,3,4-trihydroxyoctadecane (A) and γ -stearolactone (B). It is the first report that γ -stearolactone (B) is isolated from marine fungus as natural product.
文摘Twenty patients with diabetes type-2, aged between 38 and 61 years, with at least one cardiovascular risk factor were divided in two groups (Group-1 included newly diagnosed type 2 diabetic patients without treatment with oral antidiabetic OAD, Group-2: patients with diabetes type 2 under OAD +/- insulin (N = 11)). Patients from both groupswere taking Nicotinamide Adenine Dinucleotide (NADH) Rapid Energy 80 mg/day in two takes for a period of 56 days. A greater reduction in average fasting glucose and HbAlc after 56 days was observed in the patients of group 1 not taking metformin compared to patients of group-2 which were taking metformin. Why metformin reduces the anti-diabetic effect of NADH will be discussed.
基金supported in part by a grant from the Russian Foundation for Basic Research(Grant No.14-04-01653)
文摘Effects of two doses of the anti-diabetic drug, metformin (MF), on hormonal and metabolic levels of serum of non-diabetic male Wistar rats with 1,2-dimethylhydrazine (DMH)-induced colon tumor adenocarcinomas were studied. Carcinogenesis in the animals was also observed. Rats with DMH-induced colon adenocarcinomas had elevated levels of serum glucose, insulin, insulin- like growth factor-l, total cholesterol, triglycerides, catalase, malonic dialdehyde, glycated hemoglobin, aspartate aminotransferase, and alanine aminotransferase and decreased hemoglobin. Treatment with two doses of MF normalized maiority of these changes in DMH-treated rats, whereas the drug was ineffective in rats without DMH treatment. The only exception was the decreased triglyceride levels in MF-treated rats. A 100 mg/kg dose of MF increased DMH-induced exophytic colon carcinomas and decreased endophytic tumors compared with untreated rats. Moreover, both MF doses increased DMH-induced and highly differentiated tumors and decreased the invasiveness of colon carcinomas compared with rats provided with DMH and water. Therefore, effects of MF on metabolic homeostasis are critical for preventing colon cancer.
基金Supported by the National Eighth Five-Year Key Project of China.
文摘In order to overcome the elementary heterogeneous nucleation whileoctahydro trisodium salt of fructose- 1, 6-diphosphate (FDPNa_3·8H_2O) is crystallized with ethanol precipitation at low temperature,a new crystallization method with alcohol precipitation combined withsalt precipitation has been presented. The ethanol-sodium ac- etatesystem for crystallization of salt of fructose-1, 6-diphosphate isbased on the mechanism of crystallization of FDPNA_3·8H_2O in theethanol-low temperature system. It is found that crystal size may becontrolled by regulating Temperature of pH value of solution in thecrystallization process, and the crystal yield increases to 95/100from 78/100 Which obtained in the ethanol-low temperature system.
文摘AIM: To study the metabolic profiling of serum samples from compensated and decompensated cirrhosis patients. METHODS: A pilot metabolic profiling study was conducted using three groups: compensated cirrhosis patients (n = 30), decompensated cirrhosis patients (n = 30) and healthy controls (n = 30). A 1H nuclear magnetic resonance (NMR)-based metabonomics approach was used to obtain the serum metabolic profiles of the samples. The acquired data were processed by multivariate principal component analysis and orthogonal partial least-squares discriminant analysis (OPLS-DA). RESULTS: The OPLS-DA model was capable of distinguishing between decompensated and compensated cirrhosis patients, with an R2Y of 0.784 and a Q2Y of 0.598. Twelve metabolites, such as pyruvate, phenylala-nine and succinate, were identified as the most influential factors for the difference between the two groups. The validation of the diagnosis prediction showed that the accuracy of the OPLS-DA model was 85% (17/20). CONCLUSION: 1H NMR spectra combined with pattern recognition analysis techniques offer a new way to diagnose compensated and decompensated cirrhosis in the future.
基金Supported by The National Institute of Alcohol Abuse and Alcoholism grants AA014371 (to Joshi-Barve S),AA015970 (to McClain CJ), and Office of Dietary Supplements, NIH
文摘Alcoholism is a major health problem in the United States and worldwide,and alcohol remains the single most significant cause of liver-related diseases and deaths.Alcohol is known to influence nutritional status at many levels including nutrient intake,absorption,utilization,and excretion,and can lead to many nutritional disturbances and deficiencies.Nutrients can dramatically affect gene expression and alcohol-induced nutrient imbalance may be a major contributor to pathogenic gene expression in alcohol-induced liver disease(ALD).There is growing interest regarding epigenetic changes,including histone modifications that regulate gene expression during disease pathogenesis.Notably,modifications of core histones in the nucleosome regulate chromatin structure and DNA methylation,and control gene transcription.This review highlights the role of nutrient disturbances brought about during alcohol metabolism and their impact on epigenetic histone modifications that may contribute to ALD.The review is focused on four critical metabolites,namely,acetate,S-adenosylmethionine,nicotinamide adenine dinucleotide and zinc that are particularly relevant to alcohol metabolism and ALD.
基金Supported by the National Natural Science Foundation of China (21076216,30970046)
文摘Biodesulfurization (BDS) is a promising technology for deep desulfurization. In this work, Pseudomonas delafieldii R-8 cells are immobilized in calcium alginate beads and used for BDS of transportation fuels. It is found that thiophene and dibenzothiophene (DBT) can be simultaneously metabolized by immobilized R-8 cells. The initial sulfur content in the model oil is 300 mg·kg-1 (thiophene " DI3T= 1 " 1). After 10 h of treatment, the thiophene concentration is reduced by 40%, while DBT is reduced by 25%. The utilization rate of thiophene is faster than that of DBT. Moreover, the oil/water ratio of alginate immobilized cells is studied to reduce the water volume in desulfurization systems. Long-term recycling of BDS by alginate immobilized cells is carried out with oil/water ratio at 5 : 1. The immobilized cells are successfully reused over 15 batch cycles. In the last batch, the desulfurization activity remains at least 75% of the first batch.
基金Supported by the National Natural Science Foundation of China(30970089 200876181 20831006) the Natural Science Foundation of Guangdong Province(9351027501000003) the Project of Science and Technology of Guangdong Province(2007A010900001)
文摘Escherichia coli BW25113 was metabolically engineered for CoQ10 production by replacing ispB with ddsA from Gluconobacter suboxydans.Effects of precursor balance and reduced nicotinamide-adenine dinucleotide phosphate (NADPH) availability on CoQ10 production in E.coli were investigated.The knockout of pykFA along with pck overexpression could maintain a balance between glyceraldehyde 3-phosphate and pyruvate,increasing CoQ10 production.Replacement of native NAD-dependent gapA with NADP-dependent gapC from Clostridium acetobutylicum,together with the overexpression of gapC,could increase NADPH availability and then enhanced CoQ10 production.Three effects,overexpressions of various genes in CoQ biosynthesis and central metabolism,different vectors and culture conditions on CoQ10 production in E.coli,were all investigated.The investigation of different vectors indicated that low copy number vector may be more beneficial for CoQ10 production in E.coli.The recombinant E.coli (△ispB::ddsA,△pykFA and △gapA::gapC),harboring the two plasmids encoding pck,dxs,idi and ubiCA genes under the control of PT5 on pQE30,ispA,ddsA from Gluconobacter suboxydans and gapC from Clostridium acetobutylicum under the control of PBAD on pBAD33,could produce CoQ10 up to 3.24 mg·g-1 dry cell mass simply by changing medium from M9YG to SOB with phosphate salt and initial culture pH from 7.0 to 5.5.The yield is unprecedented and 1.33 times of the highest production so far in E.coli.
文摘Exercise affects muscle metabolism and composition in the untrained muscles. The proteome of muscle tissue will be affected by exercise and resting. This is of economic importance for pork quality where transportation relates to exercise of untrained muscles. Rest reverses exercise effects. The objective of this research was to develop potential protein biomarkers that predict the optimal resting time after exercise related to optimal pork quality. Ten litters of four female pigs were within litter allocated to the four treatment groups: exercise by running on a treadmill for 27 minutes followed by rest for 0, 1, or 3 h; control pigs without exercise. Proteome profiles and biochemical traits measuring energy metabolism and meat quality traits expected to be related to exercise were determined in the Longissimus and the Biceps femoris of the pigs. The results indicated associations between protein abundances in muscles and exercise, resting, and biochemical traits.
基金The Natural Science Foundation of China (No. 30070222)
文摘The fructose modified chitosan microcarries (CMs) were prepared by the reaction of glutaraldehyde with fructose-modified chitosan. Various factors that influence the preparation were studied and the reaction conditions were optimized. Morphology of rat hepatocytes cultured on CMs was observed using phase contrast microscope and scanning electron microscope, and the metabolic activities were measured. Rat hepatocytes cultured on CMs retained the spherical shape as they have in vivo and had high metabolic activities. Fructose can enhance the metabolic activity of hepatocytes and the modified CMs are promising scaffold for hepatocytes attachment.
文摘Statistical classification methods are frequently applied to analyze metabolomics data, especially from medicinal plants. Combined with variable selection techniques, we are able to identify marker candidates, which can be used to discriminate the group to which unknown subjects belong. After preprocessing, such as outlier checking, normalization, missing value imputation and transformation, we then mainly utilized four novel classification methods: RF (random forest), NSC (nearest shrunken centroid), PLS-DA (partial least square discriminant analysis) and SAM (significant analysis ofmicroarrays). Each method has its own device to measure the importance of single metabolite, so that, it is probable to choose highly ranked metabolites, which show the best prediction accuracy. Adapting above strategy, we have successfully analyzed several kinds of metabolomics data including Panax ginseng, Lespedeza species, Anemarrhean asphodeloides and Gastrodia elata.
基金supported by a grant from University of Texas Medical Branch National Institute of Environmental Health Sciences Center Pilot Project E506676
文摘Objective: The elevated incidence of obesity has been paralleled with higher risks of breast cancer. High adiposity increases leptin secretion from adipose tissue, which in turn increases cancer cell proliferation. The interplay between leptin and estrogen is one of the mechanisms through which leptin influences breast carcinogenesis. An unbalanced estrogen metabolism increases the formations of catechol estrogen quinones, DNA adducts, and cancer mutations. This study aims to investigate the effect of leptin on some estrogen metabolic enzymes and DNA adduction in breast cancer cells.Methods: High performance liquid chromatography(HPLC) was performed to analyze the DNA adducts 4-OHE1[E2]-1-N3 adenine and 4-OHE1[E2]-1-N7 guanine. Reporter gene assay, real time reverse transcription polymerase chain reaction(real time RT-PCR), and Western blot were used to assess the expression of estrogen metabolizing genes and enzymes: Cytochrome P-4501B1(CYP1B1), Nicotinamide adenine dinucleotide phosphate-quinone oxidoreductase1(NQO1), and Catechol-O-methyl transferase(COMT).Results: Leptin significantly increased the DNA adducts 4-OHE1[E2]-1-N3 adenine and 4-OHE1[E2]-1-N7 guanine.Furthermore, leptin significantly upregulated CYP1B1 promoter activity and protein expression. The luciferase promoter activities of NQO1 and m RNA levels were significantly reduced. Moreover, leptin greatly reduced the reporter activities of the COMT-P1 and COMT-P2 promoters and diminished the protein expression of COMT.Conclusions: Leptin increases DNA adduct levels in breast cancer cells partly by affecting key genes and enzymes involved in estrogen metabolism. Thus, increased focus should be directed toward leptin and its effects on the estrogen metabolic pathway as an effective approach against breast cancer.
基金National Natural Science Foundation of China (Grant No.30873170)the National Basic Research Program of China(973 Program 2007CB935800 and 2009CB930300)
文摘Mitochondria are increasingly recognized as important targets for tumor treatment because of their central roles in apoptotic pathways and cellular metabolism. Dichloroacetate (DCA), a low molecular weight mitochondria-targeting agent, exhibits potential therapeutic effects for tumors. Based on the effects of DCA on tumor cellular metabolism, we carried out this study to investigate the anti-tumor activity of DCA in C6 glioma cells in vitro. The results showed that DCA was able to increase the activity of pyruvate dehydrogenase (PDH), induce the production of reactive oxygen species (ROS) and reduce the mitochondrial membrane potential (MMP) in C6 ceils in vitro (P〈0.05 or 0.01), indicating that the anti-tumor effects of DCA in C6 cells could be through the activation of the mitochondrial pathway. In conclusion, mitochondria could be a viable therapeutic target for the treatment of glioma.
基金Supported by the National Natural Science Foundation of China (No. 30970101)
文摘The effects of carbon (C) and nitrogen (N) sources on N utilization and biosynthesis of amino acids were examined in the germinating spores of the arbuscular mycorrhizal (AM) fungus Glomus intraradices Schenck & Smith after exposure to various N substrates, CO2, glucose, and/or root exudates. The N uptake and de novo biosynthesis of amino acids were analyzed using stable isotopic labeling with mass spectrometric detection. High-performance liquid chromatography-based analysis was used to measure amino acid levels. In the absence of exogenous N sources and in the presence of 25 mL L^-1 CO2, the germinating AM fungal spores utilized internal N storage as well as C skeletons derived from the degradation of storage lipids to biosynthesize the free amino acids, in which serine and glycine were produced predominantly. The concentrations of internal amino acids increased gradually as the germination time increased from 0 to 1 or 2 weeks. However, asparagine and glutamine declined to the low levels; both degraded to provide the biosynthesis of other amino acids with C and N donors. The availability of exogenous inorganic N (ammonium and nitrate) and organic N (urea, arginine, and glutamine) to the AM fungal spores using only CO2 for germination generated more than 5 times more internal free amino acids than those in the absence of exogenous N. A supply of exogenous nitrate to the AM fungal spores with only CO2 gave rise to more than 10 times more asparagine than that without exogenous N. In contrast, the extra supply of exogenous glucose to the AM fungal spores generated a significant enhancement in the uptake of exogenous N sources, with more than 3 times more free amino acids being produced than those supplied with only exogenous CO2. Meanwhile, arginine was the most abundant free amino acid produced and it was incorporated into the proteins of AM funsal spores to serve as an N storage compound.
基金Project supported by Punjab Agricultural Research Board (PARB)the project No.150 awarded to Dr.Iqrar Ahmad KHAN,Pakistan
文摘Good quality deoxyribonucleic acid (DNA) is the pre-requisite for its downstream applications. The presence of high concentrations of polysaccharides, polyphenols, proteins, and other secondary metabolites in mango leaves poses problem in getting good quality DNA fit for polymerase chain reaction (PCR) applications. The problem is exacerbated when DNA is extracted from mature mango leaves. A reliable and modified protocol based on the cetyl trimethylammonium bromide (CTAB) method for DNA extraction from mature mango leaves is described here. High concentrations of inert salt were used to remove polysaccharides; Polyvinylpyrrolidone (PVP) and 13-mercaptoethanol were employed to man'age phenolic compounds. Extended chloroform-isoamyl alcohol treatment followed by RNase treatment yielded 950-1050 pg of good quality DNA, free of protein and RNA. The problems of DNA degradation,contamination, and low yield due to irreversible binding of phenolic compounds and coprecipitation of polysaccharides with DNA were avoided by this method, The DNA isolated by the modified method showed good PCR amplification using simple sequence repeat (SSR) primers, This modified protocol can also be used to extract DNA from other woody plants having similar problems.
基金Basic Research Expense of China Academy of TCM(ZZ2006088)National Nature Science Foundation of China(50732307)
文摘Objective: To observe the influence of transcutaneous CO2 emission (TCE) at points on the meridian or beside the meridian after different stimulations like acupuncture De-qi, sham acupuncture, study the correlation between acupuncture De-qi and local energy metabolism through TCE. Methods: Twenty healthy volunteers (male 8, female 12, average age 29 years old) were selected. Before, during and after five different acupuncture Neiguan (PC 6), the TCE was measured at Quze (PC 3), point A [at the lower one fourth of line between Tianquan (PC 2) and Quze (PC 3)] , point B [at the middle of line between Ximen (PC 4) and Quze (PC 3)], point C (2 cm ulnar side point A) and point D (2 cm ulnar side point B) with a high sensitive CO2 instrument (Frewil-Q.F., made in China). The measure results were compared. Results: The comparison on value of TCE before and after the acupuncture, in Sham acupuncture and shallow acupuncture groups, it increased in all five points; in De-qi acupuncture group, there are significant increase on point A, point B, and Quze (PC 3), it has statistic significance, but there are no significant increase on point C and D. After Ximen (PC 4) or Daling (PC 7) were pressed to block Neiguan (PC 6), the value of TCE on Quze (PC 3), point A and point B were decreased during acupuncture Neignan (PC 6), and increased after the block was removed, but there was no significant difference. Conclusion: Sham acupuncture has also some effects on body, it can increase energy metabolism of local skin, it may be the reason that shallow acupuncture without qi arriving can obtain clinical efficacy. The operation method of traditional qi arriving acupuncture can increase energy metabolism of relevant meridian skin, mechanical press can reduce this effect.
基金National Natural Science Foundation of China(Grant No.21562033)
文摘The peroxisome proliferator-activated receptors (PPARs), PPARt,, PPARβ/δ and PPARy, are ligand-activated transcriptional factors, which belong to the nuclear receptor super family and play crucial roles in glucose and lipid metabolism. Based on the impressive advantages ofPPAR agonists (like TZD and fibrate compounds) in the treatment of metabolic syndrome and type 2 diebetes, PPAR modulators have doubtlessly grabbed much more attention. However, serious clinical adverse effects, especially for PPARy agonists, hinder the development of PPAR agonist, Therefore, the selectivity and safety would be the key points and have been taken into the consideration for novel generation PPAR agonist research, and then several dual- or pan-PPAR modulators have emerged. Furthermore, experimental study indicates that partial agonists can neutralize the side effect and achieve modest therapeutic effect. This review summaries structural features of PPAR receptors, illustrates the method of PPAR modulator design, then lists and analyzes recent dual- and nan- agonists