RESUMO
Environmental exposures are the main cause of cancer, and their carcinogenicity has not been fully evaluated, identifying potential carcinogens that have not been evaluated is critical for safety. This study is the first to propose a weight of evidence (WoE) approach based on computational methods to prioritize potential carcinogens. Computational methods such as read across, structural alert, (Quantitative) structure-activity relationship and chemical-disease association were evaluated and integrated. Four different WoE approach was evaluated, compared to the best single method, the WoE-1 approach gained 0.21 and 0.39 improvement in the area under the receiver operating characteristic curve (AUC) and Matthew's correlation coefficient (MCC) value, respectively. The evaluation of 681 environmental exposures beyond IARC list 1-2B prioritized 52 chemicals of high carcinogenic concern, of which 21 compounds were known carcinogens or suspected carcinogens, and eight compounds were identified as potential carcinogens for the first time. This study illustrated that the WoE approach can effectively complement different computational methods, and can be used to prioritize chemicals of carcinogenic concern.
Assuntos
Carcinógenos , Exposição Ambiental , Humanos , Carcinógenos/toxicidade , Exposição Ambiental/efeitos adversos , Relação Quantitativa Estrutura-Atividade , Medição de Risco , AnimaisRESUMO
Folic acid (FA) has been reported to inhibit astrocyte apoptosis and improve aging-induced disorders; however, its role in telomere attrition remains unclear. In present study, 4-month-old senescence-accelerated mouse prone 8 (SAMP8) mice were assigned to four treatment groups for the in vivo experiment: FA-deficient diet (FA-D) group, FA-normal diet (FA-N) group, low FA-supplemented diet (FA-L) group, and high FA-supplemented diet (FA-H) group. These mice were euthanized when 10 months old. There was also a young SAMP8 (4 months old) control group (Con-Y) fed with FA-normal diet. In in vitro study, primary cultures of astrocytes from hippocampus and cerebral cortex were incubated for five generations with various concentrations of FA (0-40 µM) and were assigned to five groups: FA 0 µM (generation 5), FA 10 µM (generation 5), FA 20 µM (generation 5), FA 40 µM (generation 5), and FA 10 µM (generation 1). The results showed that FA supplementation inhibited aging-induced astrocytosis, astrocyte apoptosis, neurodegeneration, and prevented telomere attrition in hippocampus and cortex of SAMP8 mice. FA supplementation also decreased apoptosis and telomere attrition, and increased telomerase activity, in primary cultures of astrocytes. These results showed that it may be one of the mechanisms that FA inhibiting aging-induced apoptosis of astrocyte by alleviating telomere attrition.
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Astrócitos , Ácido Fólico , Envelhecimento , Animais , Apoptose , Ácido Fólico/farmacologia , Camundongos , TelômeroRESUMO
Cucumber is one of the most widely cultivated greenhouse vegetables, and its quality and yield are threatened by drought stress. Studies have shown that carbon dioxide concentration ([CO2]) enrichment can alleviate drought stress in cucumber seedlings; however the mechanism of this [CO2] enrichment effect on root drought stress is not clear. In this study, the effects of different drought stresses (simulated with 0, 5% and 10% PEG 6000, i.e., no, moderate, and severe drought stress) and [CO2] (400 µmol·mol-1 and 800 ± 40 µmol·mol-1) on the cucumber seedling root proteome were analyzed using the tandem mass tag (TMT) quantitative proteomics method. The results showed that after [CO2] enrichment, 346 differentially accumulating proteins (DAPs) were found only under moderate drought stress, 27 DAPs only under severe drought stress, and 34 DAPs under both moderate and severe drought stress. [CO2] enrichment promoted energy metabolism, amino acid metabolism, and secondary metabolism, induced the expression of proteins related to root cell wall and cytoskeleton metabolism, effectively maintained the balance of protein processing and degradation, and enhanced the cell wall regulation ability. However, the extent to which [CO2] enrichment alleviated drought stress in cucumber seedling roots was limited under severe drought stress, which may be due to excessive damage to the seedlings.
Assuntos
Cucumis sativus , Plântula , Plântula/metabolismo , Cucumis sativus/metabolismo , Proteômica/métodos , Dióxido de Carbono/metabolismo , Secas , Estresse Fisiológico , Raízes de Plantas/metabolismo , Proteínas de Plantas/metabolismoRESUMO
INTRODUCTION: The main objective of this study was to explore the mechanism of nicotine improving cognitive impairments in ischemic rats. METHODS: Twenty adult male Sprague-Dawley (SD) rats underwent ischemic model surgery by injecting endothelin-1 into the left thalamus, which were classified into four different groups with different intervention: nicotine (1.5 mg/kg/d), dihydro-ß-erythroidine (DHßE; 3 mg/kg/d), nicotine (1.5 mg/kg/d) + DHßE (3 mg/kg/d), or saline, after ischemic model surgery. Another five male SD rats also underwent same surgery, while not injecting endothelin-1 but saline, as the control group. Morris water maze (MWM) test was adopted to assess the cognition. All the rats underwent the MWM test, micro positron emission tomography imaging with 2-[18F]-A-85380, and messenger RNA (mRNA) test of αâ4 nicotinic acetylcholine receptor (nAChR), ßâ2 nAChR, tumor necrosis factor-alpha (TNF-α), IL-1ß, and IL-6. RESULTS: The MWM test showed the rats given nicotine showing better memory than ischemic rats (p < .05), whereas the rats given DHßE or both nicotine and DHßE did not show any statistical difference from the ischemic rats (p > .05). Micro positron emission tomography imaging showed higher uptake of tracer in the left thalamus and whole brain in rats given nicotine than in ischemic rats, but the rats given DHßE or both nicotine and DHßE did not. By real-time PCR test, the mRNA of αâ4 nAChR and ßâ2 nAChR in rats given nicotine increased significantly compared with ischemic rats and decreased TNF-α, IL-1ß, and IL-6 mRNA (all ps < .05). CONCLUSIONS: By activating αâ4ßâ2 nAChRs, nicotine plays a role in inhibiting the inflammatory factors, which contributes to improving cognitive impairment in ischemic rats. IMPLICATIONS: It is well acknowledged that vascular cognitive impairment (VCI) is the second most common cause of dementia after Alzheimer's disease. Cholinergic agents have potential for the symptomatic treatment of the cognitive symptoms of dementia, but the exact mechanism still remains unclear. There are potential complex associations and interactions between VCI and inflammation. This study showed that nicotine had anti-inflammatory potency, which is most likely because of the activation of the nAChRs. By activating α4ß2 nAChRs, nicotine played a role in inhibiting the inflammatory factors, which contribute to improving cognitive impairment in ischemic rats.
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Inflamação/prevenção & controle , Isquemia/complicações , Transtornos Neurocognitivos/prevenção & controle , Nicotina/administração & dosagem , Agonistas Nicotínicos/farmacologia , Antagonistas Nicotínicos/farmacologia , Receptores Nicotínicos/metabolismo , Animais , Di-Hidro-beta-Eritroidina/farmacologia , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/patologia , Isquemia/patologia , Masculino , Transtornos Neurocognitivos/etiologia , Transtornos Neurocognitivos/metabolismo , Transtornos Neurocognitivos/patologia , Ratos , Ratos Sprague-DawleyRESUMO
Elevated atmospheric CO2 alleviates moderate to severe drought stresses at physiological level in cucumber. To investigate the underlying metabolic mechanisms, cucumber seedlings were treated with two [CO2] and three water treatments combinations, and their leaves were analyzed using a non-targeted metabolomics approach. The results showed that elevated [CO2] changed 79 differential metabolites which were mainly associated with alanine, aspartate and glutamate metabolism; arginine and proline metabolism; TCA cycle; and glycerophospholipid metabolism under moderate drought stress. Moreover, elevated [CO2] promoted the accumulation of secondary metabolites; including isoferulic acid, m-coumaric acid and salicyluric acid. Under severe drought stress, elevated [CO2] changed 26 differential metabolites which mainly involved in alanine, aspartate and glutamate metabolism; pyruvate metabolism; arginine and proline metabolism; glyoxylate and dicarboxylate metabolism; cysteine and methionine metabolism; starch and sucrose metabolism; glycolysis or gluconeogenesis; and pyrimidine metabolism. In addition, elevated [CO2] accumulated carbohydrates, 1,2,3-trihydroxybenzene, pyrocatechol, glutamate, and l-gulonolactone, to allow adaption to severe drought. In conclusion, the metabolites and metabolic pathways associated with the alleviation of drought stresses by elevated [CO2] were different according to the level of drought stress. Our results may provide a theoretical basis for CO2 fertilization and application of exogenous metabolites to enhance drought tolerance of cucumber.
Assuntos
Pressão Atmosférica , Dióxido de Carbono/metabolismo , Cucumis sativus/metabolismo , Secas , Metabolômica , Folhas de Planta/metabolismo , Plântula/metabolismo , Dióxido de Carbono/análiseRESUMO
BACKGROUND: Supplementation with Selenium (Se) has been shown to lower blood cholesterol and increase tissue concentrations of the antioxidant glutathione (GSH); however, the effects of Se supplementation, in combination with supplemental magnesium, on high fat-induced hyperlipidemia have not been studied. This study was designed to elucidate the effects of oral selenium and magnesium co-supplementation on antihyperlipidemic and hepatoprotective, antioxidative activities, and related gene expression in a hyperlipidemic rat model. METHODS: Forty male Sprague Dawley rats were divided into 4 groups: one group served as control group (CT), provided control diet; The other groups were made hyperlipidemic with high-fat diet; specifically, a high-fat diet group (HF); low-dose selenium (0.05 mg/kg·bw) + low-dose magnesium (5.83 mg/kg·bw) supplement high-fat diet group (HF + LSe + LMg) and high-dose selenium (0.10 mg/kg·bw) + high-dose magnesium (58.33 mg/kg·bw) supplement high-fat diet group (HF + HSe + HMg). The first 4 weeks of the experiment was a hyperlipidemia inducing period using high-fat diet and the following 8 weeks involved in selenium and magnesium co-supplementation. On day 0, 20, 40 and 60 of the intervention, lipid profile was measured. At the end of the 12-week experiments, final blood and liver samples were collected for the measurements of lipid profile, antioxidative indexes, pathological examination, and liver lipid metabolism related gene expression. RESULTS: The elevated levels of serum and liver total cholesterol (TC) and serum LDL-C induced by feeding high-fat diets were significantly reduced by low-dose Se and Mg co-supplementation. Both doses of selenium and magnesium co-supplementation notably decreased the blood and liver TG levels, liver function indexes ALT and AST and the ratio of TC/HDL-C and TG/HDL-C. In contrast, Se and Mg supplementation showed a substantial increase in Se-dependent glutathione peroxidase (GSH-Px) and SOD activities and an significant reduce of level of MDA of hyperlipidemic rats. Oil Red O staining showed that selenium and magnesium co-supplementation significantly reduced hepatic intracellular triacylglycerol accumulation. H&E staining also showed that selenium and magnesium co-supplementation can attenuate liver steatosis. Selenium and magnesium co-supplementation remarkably inhibited the mRNA expression level of hepatic lipogenesis genes liver X receptor alpha (LXRα),SREBP-1c and FASN (fatty acid synthase), regulated the mRNA expression levels of liver enzymes related to cholesterol metabolism, including the down regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) and the upregulation of cholesterol 7α-hydroxylase (CYP7A1) and lecithin cholesterol acyltransferase (LCAT) in the liver of hyperlipidemia rats. CONCLUSIONS: Oral selenium and magnesium co-supplementation inhibited an increase of lipid and liver profile and liver function index induced by a high-fat diet, and enhanced the activity of the antioxidant enzymes. Selenium combined with magnesium is a promising therapeutic strategy with lipid-lowering and antioxidative effects that protects the liver against hyperlipidemia.
Assuntos
Dieta Hiperlipídica/efeitos adversos , Gluconatos/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Selenito de Sódio/farmacologia , Administração Oral , Animais , Antioxidantes/metabolismo , Peso Corporal/efeitos dos fármacos , Suplementos Nutricionais , Enzimas/genética , Enzimas/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Gluconatos/administração & dosagem , Metabolismo dos Lipídeos/genética , Lipídeos/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Ratos Sprague-Dawley , Selenito de Sódio/administração & dosagemRESUMO
3-Ketosteroid-Δ1-dehydrogenases (KstDs [EC 1.3.99.4]) catalyze the Δ1-dehydrogenation of steroids and are a class of important enzymes for steroid biotransformations. In this study, we cloned 12 putative KstD-encoding (kstd) genes from both fungal and Gram-positive microorganisms and attempted to overproduce the recombinant proteins in E. coli BL21(DE3). Five successful recombinant enzymes catalyzed the Δ1-desaturation of a variety of steroidal compounds such as 4-androstene-3,17-dione (AD), 9α-hydroxy-4-androstene-3,17-dione (9-OH-AD), hydrocortisone, cortisone, and cortexolone. However, the substrate specificity and catalytic efficiency of the enzymes differ depending on their sources. The purified KstD from Mycobacterium smegmatis mc2155 (MsKstD1) displayed high catalytic efficiency toward hydrocortisone, progesterone, and 9-OH-AD, where it had the highest affinity (K m 36.9 ± 4.6 µM) toward 9-OH-AD. On the other hand, the KstD from Rhodococcus erythropolis WY 1406 (ReKstD) exhibited high catalytic efficiency toward androst-4,9(11)-diene-3,17-dione (Diene), 21-acetoxy-pregna-4,9(11),16-triene-3,20-dione (Triene), and cortexolone, where in all three cases the K m values (12.3 to 17.8 µM) were 2.5-4-fold lower than that toward hydrocortisone (46.3 µM). For both enzymes, AD was a good substrate although ReKstD had a 3-fold higher affinity than MsKstD1. Reaction conditions were optimized for the biotransformation of AD or hydrocortisone in terms of pH, temperature, and effects of hydrogen peroxide, solvent, and electron acceptor. For the biotransformation of hydrocortisone with 20 g/L wet resting E. coli cells harboring MsKstD1 enzyme, the yield of prednisolone was about 90% within 3 h at the substrate concentration of 6 g/L, demonstrating the application potential of the newly cloned KstDs.
Assuntos
Biotransformação , Mycobacterium smegmatis/enzimologia , Oxirredutases/genética , Oxirredutases/metabolismo , Rhodococcus/enzimologia , Esteroides/metabolismo , Proteínas de Bactérias/genética , Catálise , Clonagem Molecular , Cortisona/metabolismo , Escherichia coli/genética , Hidrocortisona/metabolismo , Mycobacterium smegmatis/genética , Oxirredutases/química , Oxirredutases/isolamento & purificação , Prednisolona/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Rhodococcus/genética , Especificidade por SubstratoRESUMO
Amblyopia is the common disease in the children's growth. There are some disadvantages in traditional treatment to amblyopia, such as poor compliance, easily leading to the healthy eye eyesight problem, the poor recovery of binocular and stereoscopy vision, etc. This paper put forward a new individual amblyopia treatment system to solve these problems. It combined pattern reversal visual evoked potential (P_VEP) feedback and dichoptic training theory and then developed the EEG data acquisition and synchronized trigger circuit using and I/O data collecting card, realized the raw EEG signal real-time sampling, extracted VEP waveform from the raw EEG data by using digital filtering algorithm, average superposition algorithm and wavelet an lgorithm, finally, the latency and peak of P_VEP wave shape were accurately measured. This system also present an individual treatment solution based on dichoptic training model by searching and obtaining the best spatial frequency of the treatment training picture and combining with 3D display technology.
Assuntos
Algoritmos , Ambliopia/terapia , Potenciais Evocados Visuais , Criança , Humanos , Visão Binocular , Acuidade VisualRESUMO
Compared to (S)-selective amine transaminase ((S)-AT), the (R)-selective counterpart ((R)-AT) has been less studied. As such, a simplified "Motif Sequence Blast" search (Höhne et al. Nat Chem Biol 6:807-813, 2010) was carried out to identify new (R)-ATs from the protein databases. The combined conserved sequence motifs of (R)-ATs based on the previous in silico method of predicting (R)-selective amine transaminase were used as the template sequence for BLASTP search at default settings in NCBI, and six candidate sequences were identified. These putative (R)-AT genes were synthesized and overexpressed in Escherichia coli. Among them, five new (R)-ATs were expressed as soluble protein and showed unusual substrate specificity and high stereoselectivity. Furthermore, several unnatural amino acids, such as D-alanine, D-2-aminobutyric acid, and D-norvaline, were synthesized via the (R)-AT-catalyzed amino transfer reaction to the corresponding keto acids. Optically pure (S)-amines were also obtained by kinetic resolution of racemic amines catalyzed with these new (R)-ATs. Therefore, the Motif Sequence Blast search offers a quick and effective method for in silico identification of new (R)-ATs, and the newly identified (R)-ATs are attractive additions to the toolbox of (R)-ATs for further study and industrial application.
Assuntos
Transaminases/genética , Transaminases/metabolismo , Alanina/metabolismo , Aminobutiratos/metabolismo , Cordyceps/genética , Cordyceps/metabolismo , Bases de Dados de Proteínas , Fusarium/genética , Fusarium/metabolismo , Cetoácidos/metabolismo , Nectria/genética , Nectria/metabolismo , Estrutura Terciária de Proteína , Especificidade por Substrato , Trichoderma/genética , Trichoderma/metabolismo , Valina/análogos & derivados , Valina/metabolismoRESUMO
Wild-type meso-diaminopimelate dehydrogenase (DAPDH) is usually specific to the native substrate, meso-2,6-diaminopimelate. Recently, a DAPDH from Symbiobacterium thermophilum (StDAPDH) was found to exhibit expanded substrate specificity. As such, its crystal structures in apo form and in complex with NADP(+) and both NADPH and meso-DAP were investigated to reveal the structural basis of its unique catalytic properties. Structural analysis results show that StDAPDH should prefer an ordered kinetic catalytic mechanism. A second substrate entrance tunnel with Met152 at its bottleneck was found, through which pyruvate/D-alanine might bind and enter the catalytic cavity, providing some structural insights into its high activity toward pyruvate. The side chain of Met152 might interact with Asp92 and Asn253, thus affecting the domain motion and catalysis. These results offer useful information for understanding the unique catalytic properties of StDAPDH and guiding further engineering of this enzyme.
Assuntos
Aminoácido Oxirredutases/química , Aminoácido Oxirredutases/metabolismo , Gammaproteobacteria/enzimologia , Mutação , Aminoácido Oxirredutases/genética , Modelos Moleculares , Mutagênese , Conformação Proteica , Especificidade por SubstratoRESUMO
A cyclohexylamine oxidase (CHAO) of bacterial origin was previously shown to be a potentially useful catalyst in the deracemization of racemic primary amines. To further explore the properties and application of this enzyme, five single-amino acid substitution mutants (L199A, M226A, Y321A, Y321F, and L353M) were created based on superimposition of the tertiary structure of CHAO and the monoamine oxidase (MAO) B homolog. The substrate specificity of the purified wild-type and five mutant enzymes were examined towards 38 structurally diverse amines. All the enzymes exhibited better activity for primary amines than secondary and tertiary amines and in general exhibited high stereoselectivity. Among the mutant enzymes, M226A displayed an enhanced activity (5-400%) towards most substrates, and L353M showed 7-445% higher activity towards primary aliphatic amines with cycloalkane or aromatic moieties. Kinetic parameters revealed that both Y321 mutants showed higher catalytic efficiency towards cyclooctanamine, whereas the wild-type CHAO (wt CHAO) was most efficient towards cyclohexylamine. The wt CHAO or variant L353M in combination with a borane-ammonia complex as reducing agent was applied to the deracemization of 1-aminotetraline to give the (R)-enantiomer, a precursor of an antidepressant drug Norsertraline, in good yield (73-76%), demonstrating their application potential in chiral amine synthesis.
Assuntos
Aminas/metabolismo , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/metabolismo , Aminas/química , Biocatálise , Estereoisomerismo , Especificidade por SubstratoRESUMO
11ß-Hydrocortisone (11ß-HC) is an important anti-inflammatory drug and intermediate for the synthesis of other steroids. One of the methods for the synthesis of 11ß-HC is the asymmetric reduction of cortisone catalyzed by a highly regioselective and stereoselective 11ß-hydroxysteroid dehydrogenase (11ß-HSDH). However, this process has been prohibited by the poor soluble expression of the membrane-anchoring protein 11ß-HSDH in prokaryotes. To overcome this obstacle, a mutant III-1G1 (Phe80Leu/Thr105Ser/Ala260Thr/Tyr274Stop) truncated at position 274 with improved yield of soluble protein was stepwise obtained from the 11ß-HSDH from guinea pig by random mutagenesis combining with structural complementation assay and C-terminal truncating library screening. The improved 11ß-HSDH mutant and glucose dehydrogenase (GDH) from Bacillus subtilis were coexpressed in Escherichia coli. The resulting whole-cell biocatalyst catalyzed the reduction of cortisone to 11ß-HC with 98 % conversion in 20 h, laying foundation for the development of an asymmetric reduction process for the production of 11ß-HC.
Assuntos
Cortisona/metabolismo , Hidrocortisona/metabolismo , Hidroxiesteroide Desidrogenases/genética , Hidroxiesteroide Desidrogenases/metabolismo , Engenharia de Proteínas , Animais , Bacillus subtilis/enzimologia , Bacillus subtilis/genética , Biotransformação , Clonagem Molecular , Escherichia coli/genética , Escherichia coli/metabolismo , Expressão Gênica , Glucose 1-Desidrogenase/genética , Glucose 1-Desidrogenase/metabolismo , Cobaias/genética , Hidroxiesteroide Desidrogenases/química , Proteínas Mutantes/química , Proteínas Mutantes/genética , Proteínas Mutantes/metabolismo , Oxirredução , Deleção de Sequência , SolubilidadeRESUMO
OBJECTIVE: To investigate the effects of nanosized cadmium sulfide (nano-CdS) on the male reproductive system in mice. METHODS: Thirty-six specific pathogen?free male ICR mice were equally and randomly divided into three groups: two experimental groups and a control group. The two experimental groups were exposed to 100 mg/kg and 50 mg/kg nano-CdS once daily by gavage, respectively, while the control group was exposed to the same volume of physiological saline once daily by gavage. After 45 days, levels of cadmium accumulation and serum testosterone in the testis were determined, the epididymal sperm count, the rate of sperm abnormality, and histopathological changes in testis tissue were observed under a microscope, and the level of CYP11A1 mRNA was determined by qRT-PCR. RESULTS: Compared with the control group, the two experimental groups had a significantly increased level of cadmium accumulation in the testis (P < 0.05), and the 100 mg/kg nano-CdS group had a significantly decreased epididymal sperm count (P < 0.05) and a significantly increased rate of sperm abnormality (P < 0.05), but the 50 mg/kg nano-CdS group did not. The 100 mg/kg nano-CdS group showed different histopathological changes in testis tissue, but the 50 mg/kg nano-CdS group did not. The two experimental groups had significantly reduced levels of testosterone and CYP11A1 mRNA compared with the control group. CONCLUSION: Nano-CdS given through the digestive tract may have an effect on the male reproductive system in mice by affecting the key enzyme genes in the androgen synthesis pathway to reduce the levels of reproductive hormones.
Assuntos
Compostos de Cádmio/toxicidade , Sulfetos/toxicidade , Animais , Cádmio , Hormônios Esteroides Gonadais , Masculino , Camundongos , Camundongos Endogâmicos ICR , Contagem de Espermatozoides , Espermatozoides , Testículo/efeitos dos fármacos , TestosteronaRESUMO
With the incidence of neurodevelopmental disorders on the rise, it is imperative to screen and evaluate developmental neurotoxicity (DNT) compounds from a large number of environmental chemicals and understand their mechanisms. In this study, DNT qualitative structure-activity relationship (QSAR) study was carried out for the first time based on DNT data of mammals and structural characterization of DNT compounds was preliminarily illustrated. Five different classification algorithms and two feature selection methods were used to construct prediction models. The best model had good predictive ability on the external test set, but a small application domain (AD). Through combining of three different models, both MCC and AD values were improved. Furthermore, electronical properties, van der Waals volume-related properties and S, Cl or P containing substructure were found to be associated with DNT through modeling descriptors analysis and structure alerts (SAs) identification. This study lays a foundation for further DNT prediction of environmental exposures in human and contributes to the understanding of DNT mechanism.
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Total cholesterol (TC) and the cholesterol oxidation product 27-hydroxycholesterol (27-OHC) are both increased in the elderly. Accumulating evidence has linked 27-OHC to glucose metabolism in the brain, while docosahexaenoic acid (DHA) has been shown to positively regulate the 27-OHC levels. However, it is unclear whether DHA may affect glucose metabolism in the brain by regulating 27-OHC levels. In this study, we hypothesized that DHA supplementation would modulate TC levels and reduce 27-OHC levels, thereby improving brain glucose metabolism in SAMP8 mice. The mice were assigned into the Control group and DHA dietary supplementation group. The study evaluated cholesterol levels, 27-OHC levels, and glucose metabolism in the brain. The results showed that DHA supplementation decreased serum levels of TC, low-density lipoprotein cholesterol (LDL-C), and increased levels of high-density lipoprotein cholesterol (HDL-C); and improved the glucose-corrected standardized uptake value of cortex, hippocampus, and whole brain regions in SAMP8 mice. In conclusion, supplementation of DHA could regulate the cholesterol composition and reduce the level of 27-OHC, thereby improving brain glucose metabolism in SAMP8 mice.
Assuntos
Encéfalo , Ácidos Docosa-Hexaenoicos , Fluordesoxiglucose F18 , Glucose , Hidroxicolesteróis , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Animais , Ácidos Docosa-Hexaenoicos/farmacologia , Glucose/metabolismo , Camundongos , Encéfalo/metabolismo , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Hidroxicolesteróis/metabolismo , Masculino , Suplementos Nutricionais , Compostos Radiofarmacêuticos , Colesterol/metabolismo , Colesterol/sangue , HDL-Colesterol/sangueRESUMO
Medium-chain triglycerides (MCTs) and docosahexaenoic acid (DHA, Cn-3, 22:6) are essential in improving cognitive function and protecting neurocytes. This study explored the effects of the combined intervention of MCTs and DHA on inhibiting neurocyte apoptosis of the brain and improving cognitive function in senescence-accelerated mouse-prone 8 (SAMP8). Four-month-old male SAMP8 mice were randomly divided into four treatment groups (12 mice/group): DHA, MCT, DHA + MCT, and control groups, which intervened for seven months. Twelve age-matched male senescence-accelerated mouse resistant 1 (SAMR1) was used as the natural aging group. TUNEL assay and HE staining were used to assess neurocyte apoptosis and damage in the brain of mice. Moreover, the cognitive function was analyzed using the Morris water maze (MWM) and open field (OF) tests. The results showed that the cognitive function of 11-month-old SAMP8 mice decreased with age, and further pathological examination revealed the damaged neurocyte structure, karyopyknosis, cell atrophy, and even apoptosis. MCTs combined with DHA supplementation could increase octanoic acid (C8:0), decanoic acid (C10:0), and DHA levels in the serum, inhibit neurocyte apoptosis, improve neurocyte damage, moreover delay age-related cognitive decline after seven-month treatment. Furthermore, combining MCTs and DHA was significantly more beneficial than MCTs or DHA alone. In conclusion, MCTs combined with DHA could delay cognitive decline by inhibiting neurocyte apoptosis of the brain in SAMP8 mice.
Assuntos
Apoptose , Encéfalo , Cognição , Ácidos Docosa-Hexaenoicos , Triglicerídeos , Animais , Ácidos Docosa-Hexaenoicos/farmacologia , Apoptose/efeitos dos fármacos , Masculino , Cognição/efeitos dos fármacos , Camundongos , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Aprendizagem em Labirinto/efeitos dos fármacos , Suplementos Nutricionais , Envelhecimento , Teste do Labirinto Aquático de Morris/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Caprilatos/farmacologia , Modelos Animais de DoençasRESUMO
Accumulating evidence has demonstrated that medium-chain triglycerides (MCTs) and docosahexaenoic acid (DHA) positively affect cognitive function. However, it remains unclear whether the improvement is related to the alterations of gut microbiota and inflammation and the impact of the combined intervention. In this study, we hypothesized that the supplementation of MCTs combined with DHA could modulate gut microbiota, inflammation, and improve cognitive function in APPswe/PS1De9 model mice and senescence-accelerated mouse-prone-8, which are two different mouse models used in neurodegeneration research. The mice were divided into four groups: Control group, MCTs group, DHA group, and MCTs + DHA group. The study assessed cognitive function, inflammatory cytokines, and gut microbiota composition. The results showed that supplementation of MCTs + DHA improved spatial learning ability, memory capacity, exploratory behavior; decreased the relative abundance of Proteobacteria; reduced the ratio of Firmicutes/Bacteroidetes; decreased the concentrations of serum interleukin (IL)-2, IL-6, monocyte chemotactic protein-1, tumor necrosis factor-alpha, while increasing the concentration of IL-10. Furthermore, supplementation with MCTs + DHA exhibited significantly superior effects compared to MCTs or DHA alone in reducing inflammation, optimizing gut microbiota composition, and improving cognitive function. In conclusion, supplementation with MCTs + DHA improved cognition function, accompanied with favorable alterations in gut microbiota and inflammation in APPswe/PS1De9 and senescence-accelerated mouse-prone-8 mice.
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Provitamin A (Pro-VA) is necessary for human vision and immune system health, especially in growing children. The first committed step in the maize carotenoid biosynthesis pathway is catalyzed by phytoene synthase 1 (encoded by PSY1) which controls the flux of substrates into the pathway. The flow of these substrates could be directed into production of the ß-branch carotenoids (the step controlled largely by the lycopene epsilon cyclase gene), but terminated after the production of ß-carotene, rather than allowing it to be converted into the next metabolite (the step controlled largely by the ß-carotenoid hydroxylase gene). In this study, PSY1 was subjected to association mapping in two diverse maize populations, quantitative trait loci (QTL) mapping in one segregating population, and expression analysis of lines polymorphic for sites within PSY1. The results indicated that a 378-bp InDel upstream of the transcription start site and a SNP in the fifth exon resulting in a Thr to Asn substitution, explaining 7 and 8 % of the total carotenoid variation, respectively, may be functional sites associated with total carotenoid levels in maize grain. Analysis of the evolution of PSY1 strongly suggests that there was positive selection for these polymorphic sites after the divergence of yellow maize from white maize.
Assuntos
Biotecnologia/métodos , Carotenoides/biossíntese , Clima , Evolução Molecular , Variação Genética , Geranil-Geranildifosfato Geranil-Geraniltransferase/genética , Zea mays/enzimologia , Carotenoides/análise , China , Perfilação da Expressão Gênica , Estudos de Associação Genética , Mutação INDEL/genética , Polimorfismo de Nucleotídeo Único/genética , Locos de Características Quantitativas/genética , Reação em Cadeia da Polimerase em Tempo Real , Seleção Genética , Vitamina A/biossínteseRESUMO
BACKGROUND: Because human diets are composed of a wide variety of nutrients that may work synergistically to prevent or promote disease, assessing dietary nutrient intake status may be informative. The purpose of this study was to assess the dietary nutrient intake status of Chinese adults with metabolic syndrome (MetS) and to evaluate its possible role in MetS. METHODS: This case-control study was conducted from March 2010 to January 2011. A total of 123 patients with MetS and 135 controls participated in this study at the Health Examination Center of Heping District in Tianjin, China. Dietary intake was estimated by 24-h dietary recalls. We used principal component factor analysis to derive nutrient groups from 17 major nutrients. We examined the odds ratios and 95% confidence intervals using logistic regression models to test the relationship between tertiles of dietary nutrient pattern and MetS. RESULTS: There were 4 major dietary nutrient patterns in this study: "vitamin B group", "protein and lipids", "vitamin E and minerals", and "antioxidant vitamins". After adjustment for potential confounders, the highest tertile of the nutrient pattern factor score for the "vitamin B group" (odds ratio: 0.16; 95% confidence interval: 0.05-0.47) was negatively associated with MetS compared with the lowest tertiles. No relationships were found between other dietary nutrient patterns and MetS. CONCLUSIONS: The "vitamin B group" pattern was inversely associated with MetS in Chinese adults. This finding supports the hypothesis that the "vitamin B group" pattern may have a potentially beneficial effect on the prevention of MetS.
Assuntos
Povo Asiático , Ingestão de Energia , Comportamento Alimentar , Síndrome Metabólica/prevenção & controle , Adulto , Idoso , Antropometria , Antioxidantes/administração & dosagem , Biomarcadores/sangue , Estudos de Casos e Controles , China , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Gorduras na Dieta/administração & dosagem , Proteínas Alimentares/administração & dosagem , Jejum , Feminino , Humanos , Estilo de Vida , Modelos Logísticos , Masculino , Rememoração Mental , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Oligoelementos/administração & dosagem , Ácido Úrico/sangue , Complexo Vitamínico B/administração & dosagemRESUMO
Rapid development in the glutamate fermentation industry has dictated the need for effective fermentation monitoring by rapid and precise methods that provide real-time information for quality control of the end-product. In recent years, near-infrared (NIR) spectroscopy and multivariate calibration have been developed as fast, inexpensive, non-destructive and environmentally safe techniques for industrial applications. The purpose of this study was to develop models for monitoring glutamate, glucose, lactate and alanine concentrations in the temperature-triggered process of glutamate fermentation. NIR measurements of eight batches of samples were analyzed by partial least-squares regression with several spectral pre-processing methods. The coefficient of determination (R (2)), model root-mean square error of calibration (RMSEC), root-mean square error of prediction (RMSEP) and residual predictive deviation (RPD) of the test calibration for the glutamate concentration were 0.997, 3.11 g/L, 2.56 g/L and 19.81, respectively. For the glucose concentration, R (2), RMSEC, RMSEP and RPD were 0.989, 1.37 g/L, 1.29 g/L and 9.72, respectively. For the lactate concentration, R (2), RMSEC, RMSEP and RPD were 0.975, 0.078 g/L, 0.062 g/L and 6.29, respectively. For the alanine concentration, R (2), RMSEC, RMSEP and RPD were 0.964, 0.213 g/L, 0.243 g/L and 5.29, respectively. New batch fermentation as an external validation was used to check the models, and the results suggested that the predictive capacity of the models for the glutamate fermentation process was good.