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1.
Neural Regen Res ; 17(4): 875-880, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34472488

RESUMO

The neutrophil-to-lymphocyte ratio (NLR) is considered a robust prognostic biomarker for predicting patient survival outcomes in many diseases. However, it remains unclear whether it can be used as a biomarker for amyotrophic lateral sclerosis (ALS). To correlate NLR with disease progression and survival in sporadic ALS, 1030 patients with ALS between January 2012 and December 2018 were included in this study. These patients were assigned into three groups according to their NLR values: Group 1 (NLR < 2, n = 544 [52.8%]), Group 2 (NLR = 2-3, n = 314 [30.5%]), and Group 3 (NLR > 3, n = 172 [16.7%]). All patients were followed up until April 2020. Patients in Group 3 had a significantly older onset age, a lower score on the Revised ALS Functional Rating Scale, and rapidly progressing disease conditions. Furthermore, faster disease progression rates were associated with higher NLR values (odds ratio = 1.211, 95% confidence interval [CI]: 1.090-1.346, P < 0.001) after adjusting for other risk factors. Compared with Groups 1 and 2, the survival time in Group 3 was significantly shorter (log-rank P = 0.002). The NLR value was considered an independent parameter for the prediction of survival in ALS patients after normalizing for all other potential parameters (hazard ratio [HR] = 1.079, 95% CI: 1.016-1.146, P = 0.014). The effects on ALS survival remained significant when adjusted for treatment (HR = 1.074, 95% CI: 1.012-1.141, Ptrend = 0.019) or when considering the stratified NLR value (HR = 1.115, 95% CI: 1.009-1.232, Ptrend = 0.033). Thus, the NLR may help to predict the rate of disease progression and survival in patients with sporadic ALS. The study was approved by the Institutional Ethics Committee of West China Hospital of Sichuan University, China (approval No. 2015 (236)) on December 23, 2015.

2.
J Nutr Biochem ; 99: 108843, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34407449

RESUMO

Epigallocatechin-3-gallate (EGCG), the main active ingredient of green tea, exhibits low toxic side effect and versatile bioactivities, and its anti-cancer effect has been extensively studied. Most of the studies used cancer cell lines and xenograft models. However, whether EGCG can prevent tumor onset after cancer-associated mutations occur is still controversial. In the present study, Krt14-cre/ERT-Kras transgenic mice were developed and the expression of K-RasG12D was induced by tamoxifen. Two weeks after induction, the K-Ras mutant mice developed exophytic tumoral lesions on the lips and tongues, with significant activation of Notch signaling pathway. Administration of EGCG effectively delayed the time of appearance, decreased the size and weight of tumoral lesions, relieved heterotypic hyperplasia of tumoral lesions, and prolonged the life of the mice. The Notch signaling pathway was significantly inhibited by EGCG in the tumoral lesions. Furthermore, EGCG significantly induced cell apoptosis and inhibited the proliferation of tongue cancer cells by blocking the activation of Notch signaling pathway. Taken together, these results indicate EGCG as an effective chemotherapeutic agent for tongue cancer by targeting Notch pathway.

3.
Front Physiol ; 12: 724470, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34483973

RESUMO

Cardiac fibrosis is evident even in the situation without a significant cardiomyocyte loss in diabetic cardiomyopathy and a high glucose (HG) level independently activates the cardiac fibroblasts (CFs) and promotes cell proliferation. Mitochondrial respiration and glycolysis, which are key for cell proliferation and the mitochondria-associated membranes (MAMs), are critically involved in this process. However, the roles and the underlying mechanism of MAMs in the proliferation of HG-induced CFs are largely unknown. The proliferation and apoptosis of CFs responding to HG treatment were evaluated. The MAMs were quantified, and the mitochondrial respiration and cellular glycolytic levels were determined using the Seahorse XF analyzer. The changes of signal transducer and activator of transcription 3 (STAT3) and mitofusin-2 (MFN2) in responding to HG were also determined, the effects of which on cell proliferation, MAMs, and mitochondrial respiration were assessed. The effects of STAT3 on MFN2 transcription was determined by the dual-luciferase reporter assay (DLRA) and chromatin immunoprecipitation (CHIP). HG-induced CFs proliferation increased the glycolytic levels and adenosine triphosphate (ATP) production, while mitochondrial respiration was inhibited. The MAMs and MFN2 expressions were significantly reduced on the HG treatment, and the restoration of MFN2 expression counteracted the effects of HG on cell proliferation, mitochondrial respiration of the MAMs, glycolytic levels, and ATP production. The mitochondrial STAT3 contents were not changed by HG, but the levels of phosphorylated STAT3 and nuclear STAT3 were increased. The inhibition of STAT3 reversed the reduction of MFN2 levels induced by HG. The DLRA and CHIP directly demonstrated the negative regulation of MFN2 by STAT3 at the transcription levels via interacting with the sequences in the MFN2 promoter region locating at about -400 bp counting from the start site of transcription. The present study demonstrated that the HG independently induced CFs proliferation via promoting STAT3 translocation to the nucleus, which switched the mitochondrial respiration to glycolysis to produce ATP by inhibiting MAMs in an MFN2-depression manner.

4.
J Med Genet ; 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34544842

RESUMO

BACKGROUND: A large number of new causative and risk genes for amyotrophic lateral sclerosis (ALS) have been identified mostly in patients of European ancestry. In contrast, we know relatively little regarding the genetics of ALS in other ethnic populations. This study aims to provide a comprehensive analysis of the genetics of ALS in an unprecedented large cohort of Chinese mainland population and correlate with the clinical features of rare variants carriers. METHODS: A total of 1587 patients, including 64 familial ALS (FALS) and 1523 sporadic ALS (SALS), and 1866 in-house controls were analysed by whole-exome sequencing and/or testing for G4C2 repeats in C9orf72. Forty-one ALS-associated genes were analysed. FINDINGS: 155 patients, including 26 (40.6%) FALS and 129 (8.5%) SALS, carrying rare pathogenic/likely pathogenic (P/LP) variants of ALS causative genes were identified. SOD1 was the most common mutated gene, followed by C9orf72, FUS, NEK1, TARDBP and TBK1. By burden analysis, rare variants in SOD1, FUS and TARDBP contributed to the collective risk for ALS (p<2.5e-6) at the gene level, but at the allelic level TARDBP p.Gly294Val and FUS p.Arg521Cys and p.Arg521His were the most important single variants causing ALS. Clinically, P/LP variants in TARDBP and C9orf72 were associated with poor prognosis, in FUS linked with younger age of onset, and C9orf72 repeats tended to affect cognition. CONCLUSIONS: Our data provide essential information for understanding the genetic and clinical features of ALS in China and for optimal design of genetic testing and evaluation of disease prognosis.

6.
J Parkinsons Dis ; 11(4): 1845-1855, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34250953

RESUMO

BACKGROUND: Genetic studies have indicated that variants in several lysosomal genes are risk factors for idiopathic Parkinson's disease (PD). However, the role of lysosomal genes in PD in Asian populations is largely unknown. OBJECTIVE: This study aimed to analyze rare variants in lysosomal related genes in Chinese population with early-onset and familial PD. METHODS: In total, 1,136 participants, including 536 and 600 patients with sporadic early-onset PD (SEOPD) and familial PD, respectively, underwent whole-exome sequencing to assess the genetic etiology. Rare variants in PD were investigated in 67 candidate lysosomal related genes (LRGs), including 15 lysosomal function-related genes and 52 lysosomal storage disorder genes. RESULTS: Compared with the autosomal dominant PD (ADPD) or SEOPD cohorts, a much higher proportion of patients with multiple rare damaging variants of LRGs were found in the autosomal recessive PD (ARPD) cohort. At a gene level, rare damaging variants in GBA and MAN2B1 were enriched in PD, but in SCARB2, MCOLN1, LYST, VPS16, and VPS13C were much less in patients. At an allele level, GBA p. Leu483Pro was found to increase the risk of PD. Genotype-phenotype correlation showed no significance in the clinical features among patients carrying a discrepant number of rare variants in LRGs. CONCLUSION: Our study suggests rare variants in LRGs might be more important in the pathogenicity of ARPD cases compared with ADPD or SEOPD. We further confirm rare variants in GBA are involve in PD pathogenecity and other genes associated with PD identified in this study should be supported with more evidence.

7.
Huan Jing Ke Xue ; 42(6): 3074-3083, 2021 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-34032108

RESUMO

Roxithromycin (ROX) is widespread in the water environment and has been reported to have ecotoxicological effects on aquatic organisms. To improve our understanding of these effects, we selected Daphnia magna as a test organism to study acute and chronic ROX toxicity on reproduction, growth, and antioxidant systems. The acute ROX toxicity was low, with 48 h-LC50 and 96h-LC50ROX values of 60.26 mg·L-1 and 39.81 mg·L-1, respectively. Furthermore, ROX concentrations of 0.5 µg·L-1 and 50 µg·L-1 significantly increased the frequency of egg laying, total number of eggs, and number of eggs per fetus. In the early exposure stages, ROX altered the sexual maturation time of Daphnia magna, affecting the frequency of egg laying and the number of eggs per fetus to cope with environmental stress. The intrinsic growth rate was also significantly increased by 50 µg·L-1 ROX. In both treatment groups, Daphnia magna had a shorter body length, abnormal heart rate, and inhibited swimming activity. Moreover, 50 µg·L-1 ROX inhibited the activities of POD, CAT, and GSH-Px by approximately 50% and induced MDA by more than 100%, resulting in the accumulation of reactive oxygen species in the body, which could potentially damage the cell membrane. In the 50 µg·L-1 ROX treatment, per 06 was up-regulated, enhancing the immune response of Daphnia magna. In contrast. gst and gst-theta were down-regulated, suggesting that ROX could weaken the detoxification effect of Daphnia magna. jhe, ecra, ecrb, rxr, vg1, vg2, and vit-2 were also down-regulated. ROX affected the secretion of juvenile and thyroid hormones, inhibiting the synthesis of vitellogenin. Finally, ROX also affected the growth and disturbed the population stability of Daphnia magna. This study provides a reference for the effects of ROX on the reproduction and growth of aquatic organisms and their responses at protein and gene levels.


Assuntos
Roxitromicina , Poluentes Químicos da Água , Animais , Daphnia , Oxirredução , Reprodução , Poluentes Químicos da Água/toxicidade
8.
BMC Neurol ; 21(1): 181, 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33910524

RESUMO

BACKGROUND: Camptocormia is common in patients with multiple system atrophy (MSA). The current study was aimed at assessing the frequency of camptocormia and its related factors in MSA patients with different disease durations. Also, the impact of camptocormia on disability was evaluated. METHODS: A total of 716 patients were enrolled in the study. They were classified into three groups based on disease duration (≤ 3, 3-5, ≥ 5 years). Specific scales were used to evaluate the motor and non-motor symptoms. Disease severity was assessed using the Unified Multiple System Atrophy Rating Scale (UMSARS). The binary logistic regression model was used to explore the factors related to camptocormia. To analyze the impact of camptocormia on disability in patients with disease duration less than 5 years, propensity score matching (PSM) and stratified Cox regression analysis were used. RESULTS: In the current study, we found that the frequency of camptocormia was 8.9, 19.7 and 19.2% when the disease duration was ≤3, 3-5, ≥ 5 years, respectively. In the disease duration ≤3 years group, we found that MSA-parkinsonian subtype (MSA-P) (OR = 2.043, P = 0.043), higher total UMSARS score (OR = 1.063, P < 0.001), older age of onset (OR = 1.047, P = 0.042), and lower score on the frontal assessment battery (FAB) (OR = 0.899, P = 0.046) were associated with camptocormia. Only greater disease severity was associated with camptocormia in the group of patients with disease duration 3-5 years (OR = 1.494, P = 0.025) and in the group of patients with disease duration ≥5 years (OR = 1.076, P = 0.005). There was no significant impact of camptocormia on disability in patients with a disease duration of < 5 years (HR = 0.687, P = 0.463). CONCLUSION: The frequency of camptocormia increased with prolonged disease duration. Disease severity was related to camptocormia at different stages of the disease. The MSA-P subtype, older age of onset, and lower FAB score were associated with camptocormia in the early stage of the disease.


Assuntos
Atrofia de Múltiplos Sistemas/complicações , Atrofia Muscular Espinal/etiologia , Curvaturas da Coluna Vertebral/etiologia , Idade de Início , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Atrofia Muscular Espinal/epidemiologia , Fatores de Risco , Índice de Gravidade de Doença , Curvaturas da Coluna Vertebral/epidemiologia
9.
Mol Neurobiol ; 58(7): 3435-3442, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33723766

RESUMO

Functional and genetic studies have identified association between several Zinc finger (ZNF) proteins and Parkinson's disease (PD). However, most of them were still awaiting further replications, especially in the Asian population. Here, we systematically selected PD-relevant ZNF genes and analyzed the genetic associations between these ZNFs and PD in a large Chinese PD cohort. We identified rare variants (minor allele frequency < 0.01) in 743 unrelated patients with early-onset PD (EOPD, age at onset < 50 years) using whole exome sequencing and evaluated the association between rare variants and EOPD at both allele and gene levels. Totally 91 rare variants were identified in ZNF746, ZNF646, ZNF184, ZNF165, ZND219, and GLIS1. One variant p.R373H in ZNF219 and two variants p.G161D and p.R158H in ZNF746 were significantly associated with EOPD, and gene-based burden analysis showed enrichment of rare variants of ZNF746 in EOPD. Our findings build up the connection between ZNF746 and PD from a genetic perspective for the first time, supplement current understanding for the genetic role of ZNFs in EOPD, and broaden the mutation spectrum in PD.

10.
J Nutr Biochem ; 89: 108578, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33388352

RESUMO

The maternal nutritional status during pregnancy and lactation was closely related to the growth and development of the fetus and infants, which had a profound impact on the health of the offspring. N-3 polyunsaturated fatty acid (PUFA) had been proved to have beneficial effects on glucolipid metabolism. However, the effects of dietary different n-3 PUFA levels for mother during pregnancy and lactation on susceptibility to high-fat-diet-induced metabolic syndrome for offspring in adulthood are still unclear. The maternal mice were fed with control, n-3 PUFA-deficient or fish oil-contained n-3 PUFA-rich diets during pregnancy and lactation, and the weaned offspring were fed with high-fat or low-fat diet for 13 weeks, then were subjected to oral glucose tolerance tests. The results showed that dietary n-3 PUFA-deficiency in early life could aggravate the high-fat-diet-induced glucolipid metabolism disorders, including glucose intolerance, insulin resistance, obesity, and dyslipidemia, thus increased the susceptibility to metabolic syndrome of adult mice. Notably, nutritional supplementation with n-3 PUFA in early life could significantly alleviate the glucose metabolism disorders by increasing insulin sensitivity, inhibiting gluconeogenesis and promoting glycogenesis. In addition, administration with n-3 PUFA in early life remarkably reduced serum and hepatic lipid profiles by mediating the expression of genes related to lipogenesis and ß-oxidation of fatty acids. Dietary n-3 PUFA-deficiency in early life increases the susceptibility to metabolic syndrome of adult offspring, and nutritional supplementation with n-3 PUFA enhances the tolerance to a high-fat diet of adult offspring.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Ácidos Graxos Ômega-3/farmacologia , Fenômenos Fisiológicos da Nutrição Materna , Síndrome Metabólica/prevenção & controle , Animais , Dieta com Restrição de Gorduras , Suplementos Nutricionais , Dislipidemias/etiologia , Dislipidemias/prevenção & controle , Feminino , Óleos de Peixe/farmacologia , Intolerância à Glucose/metabolismo , Teste de Tolerância a Glucose , Resistência à Insulina , Lactação/metabolismo , Metabolismo dos Lipídeos , Lipídeos/sangue , Lipogênese , Fígado/metabolismo , Masculino , Síndrome Metabólica/etiologia , Síndrome Metabólica/patologia , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/etiologia , Obesidade/prevenção & controle , Gravidez
11.
Neural Regen Res ; 16(8): 1660-1670, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33433498

RESUMO

Patients with Parkinson's disease (PD) have impaired insulin signaling in the brain. Incretin hormones, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), can re-sensitize insulin signaling. In a recent phase II clinical trial, the first GLP-1 mimic, exendin-4, has shown reliable curative effect in patients with PD. DA-CH5 is a novel GLP-1/GIP receptor unimolecular co-agonist with a novel peptide sequence added to cross the blood-brain barrier. Here we showed that both exendin-4 and DA-CH5 protected against 6-hydroxydopamine (6-OHDA) cytotoxicity, inhibited apoptosis, improved mitogenesis and induced autophagy flux in SH-SY5Y cells via activation of the insulin receptor substrate-1 (IRS-1)/alpha serine/threonine-protein kinase (Akt)/cAMP response element-binding protein (CREB) pathway. We also found that DA-CH5 (10 nmol/kg) daily intraperitoneal administration for 30 days post-lesion alleviated motor dysfunction in rats and prevented stereotactic unilateral administration of 6-OHDA induced dopaminergic neurons loss in the substantia nigra pars compacta. However, DA-CH5 showed curative effects in reducing the levels of α-synuclein and the levels of pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-1ß). It was also more effective than exendin-4 in inhibiting apoptotic process and protecting mitochondrial functions. In addition, insulin resistance was largely alleviated and the expression of autophagy-related proteins was up-regulated in PD model rats after DA-CH5 treatment. These results in this study indicate DA-CH5 plays a therapeutic role in the 6-OHDA-unilaterally lesioned PD rat model and is superior to GLP-1 analogue exendin-4. The study was approved by the Animal Ethics Committee of Shanxi Medical University of China.

12.
Mol Neurobiol ; 58(4): 1583-1592, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33219486

RESUMO

Recent genetic studies clearly indicate that variants in several lysosomal genes act as risk factors for idiopathic Parkinson's disease (PD). Variants in the co-activator of glucocerebrosidase gene (GBA) and the four active saposins (Sap A-D) which are encoded by the prosaposin gene (PSAP) are of particular interest; however, their genetic roles in PD are unknown. Whole-exome sequencing and Sanger sequencing were used to assess the genetic etiology of 400 autosomal dominant inherited PD (ADPD) and 300 sporadic PD (SPD) patients. Variants from public databases, including Genome Aggregation Database-East Asian (GnomAD_EAS) and Chinese Millionome Database (CMDB), were used as control groups. Burden analysis based on gene and domains level were performed to investigate the role of rare PSAP variants in PD. Six rare and likely pathogenic variants, located in the Sap A-D domains, were identified and accounted for 0.75% (3/400) of ADPD and 1.33% (4/300) of SPD in the Chinese population. Based on the gene or domain, burden analysis showed that damaging missense variants in SapC had statistical significance on the risk of developing PD. Interestingly, rs4747203, an intronic variant potentially linked to PSAP expression, was associated with reduced risk for PD (p = 8.6e-7 in GnomAD EAS and p = 0.002 in Chinese). Clinically, patients carrying the likely pathogenic variants presented typical PD motor symptoms and responded well to levodopa treatment. Six out of seven patients carrying the likely pathogenic variants of PSAP presented slow disease progression, and none of the patients developed cognitive impairment. Our study expands the spectrum of mutations associated with the risk of developing PD and enhances the understanding of the relationship of the clinical phenotype of PD with PSAP variants.

13.
Neural Regen Res ; 16(3): 591-595, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32985493

RESUMO

Creatine kinase is a muscle enzyme that has been reported at various levels in different studies involving patients with amyotrophic lateral sclerosis. In the present retrospective case-control study, we included 582 patients with amyotrophic lateral sclerosis and 582 age- and sex-matched healthy controls. All amyotrophic lateral sclerosis participants received treatment in the Department of Neurology, West China Hospital, China, between May 2008 and December 2018. Serum creatine kinase levels in patients with amyotrophic lateral sclerosis were significantly higher than those in healthy controls. Subgroup analysis revealed that serum creatine kinase levels in men were higher than those in women in both amyotrophic lateral sclerosis patients and healthy controls. Compared with patients with bulbar-onset amyotrophic lateral sclerosis, patients with limb-onset amyotrophic lateral sclerosis had higher creatine kinase levels. Spearman's correlation analysis revealed that serum creatine kinase levels were not correlated with body mass index, Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised score, or progression rate. After adjusting for prognostic covariates, higher log creatine kinase values were correlated with higher overall survival in the amyotrophic lateral sclerosis patients. We also investigated the longitudinal changes in serum creatine kinase levels in 81 amyotrophic lateral sclerosis patients; serum creatine kinase levels were decreased at the second blood test, which was sampled at least 6 months after the first blood test. Together, our results suggest that serum creatine kinase levels can be used as an independent factor for predicting the prognosis of amyotrophic lateral sclerosis patients. This study received ethical approval from the Ethics Committee of West China Hospital, China (approval No. 2015(236)) on December 23, 2015.

14.
Chin Med J (Engl) ; 134(6): 690-698, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33234871

RESUMO

BACKGROUND: Sleep disorders are common but under-researched symptoms in patients with multiple system atrophy (MSA). We investigated the frequency and factors associated with sleep-related symptoms in patients with MSA and the impact of sleep disturbances on disease severity. METHODS: This cross-sectional study involved 165 patients with MSA. Three sleep-related symptoms, namely Parkinson's disease (PD)-related sleep problems (PD-SP), excessive daytime sleepiness (EDS), and rapid eye movement sleep behavior disorder (RBD), were evaluated using the PD Sleep Scale-2 (PDSS-2), Epworth Sleepiness Scale (ESS), and RBD Screening Questionnaire (RBDSQ), respectively. Disease severity was evaluated using the Unified MSA Rating Scale (UMSARS). RESULTS: The frequency of PD-SP (PDSS-2 score of ≥18), EDS (ESS score of ≥10), and RBD (RBDSQ score of ≥5) in patients with MSA was 18.8%, 27.3%, and 49.7%, respectively. The frequency of coexistence of all three sleep-related symptoms was 7.3%. Compared with the cerebellar subtype of MSA (MSA-C), the parkinsonism subtype of MSA (MSA-P) was associated with a higher frequency of PD-SP and EDS, but not of RBD. Binary logistic regression revealed that the MSA-P subtype, a higher total UMSARS score, and anxiety were associated with PD-SP; that male sex, a higher total UMSARS score, the MSA-P subtype, and fatigue were associated with EDS; and that male sex, a higher total UMSARS score, and autonomic onset were associated with RBD in patients with MSA. Stepwise linear regression showed that the number of sleep-related symptoms (PD-SP, EDS, and RBD), disease duration, depression, fatigue, and total Montreal Cognitive Assessment score were predictors of disease severity in patients with MSA. CONCLUSIONS: Sleep-related disorders were associated with both MSA subtypes and the severity of disease in patients with MSA, indicating that sleep disorders may reflect the distribution and degree of dopaminergic/non-dopaminergic neuron degeneration in MSA.


Assuntos
Atrofia de Múltiplos Sistemas , Transtorno do Comportamento do Sono REM , Estudos Transversais , Humanos , Masculino , Índice de Gravidade de Doença , Sono
15.
J Agric Food Chem ; 68(36): 9707-9717, 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32786870

RESUMO

The effect of marine-derived sea cucumber sterol (SS) with a special sulfate group on lipid accumulation remains unknown, although phytosterol has been proved to have many biological activities, including lowering blood cholesterol. The purpose of the present study is to investigate the alleviation of SS on lipid accumulation and the possible underlying mechanism using high-fat-fructose diet fed mice. Dietary administration with SS for 8 weeks reduced significantly the body weight gain and lipid levels in serum and liver. Especially, SS was superior to phytosterol in lowering lipid accumulation due to the great promotion of fatty acid ß-oxidation, the inhibition of cholesterol synthesis, and the acceleration of cholesterol efflux. The findings found that sea cucumber sterol exhibited a more significant effect than phytosterol on alleviating HFF-diet-induced lipid accumulation through regulating lipid and cholesterol metabolism, which might be attributed to the difference in the branch chain and sulfate group.


Assuntos
Cucumaria/química , Dieta Hiperlipídica/efeitos adversos , Frutose/efeitos adversos , Metabolismo dos Lipídeos/efeitos dos fármacos , Obesidade/tratamento farmacológico , Esteróis/administração & dosagem , Animais , Peso Corporal/efeitos dos fármacos , Colesterol/biossíntese , Ácidos Graxos/metabolismo , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/etiologia , Obesidade/metabolismo , Obesidade/fisiopatologia , Esteróis/química
16.
J Food Sci ; 85(7): 2207-2215, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32572979

RESUMO

Trimethylamine-N-oxide (TMAO) is considered to have negative effect on human health. Different precursors of TMAO, such as choline, betaine, and L-carnitine, are commonly found in daily foods. The aim of the present study was to compare the ability of different precursors to be metabolized into TMAO, as well as the possible effect of chronic administration with TMAO precursors on TMAO production. The rate of TMAO generation after single gavage with different precursors was L-carnitine > choline >betaine. Moreover, the serum TMAO level of mice increased more than twofold after administration with choline for 3 weeks compared with L-carnitine and betaine groups, which was accompanied by the change of intestinal flora. After the gavage of choline chloride, the production for TMAO was 2.8 and 1.6 times higher in chronic choline-treated group compared with L-carnitine and betaine groups, respectively. In addition, administration with choline increased the lowest TMAO level after intraperitoneal injection of trimethylamine (TMA) hydrochloride among the three treated groups. These findings indicated that different TMAO precursors had different ability to form TMAO in vivo, and long-term dietary intervention would affect the metabolism of precursors to generate TMA and the TMA oxidation to form TMAO, suggesting that TMAO levels in vivo could be regulated by dietary intervention. PRACTICAL APPLICATION: Diverse TMAO precursors exhibited different ability to be converted into TMAO in vivo. The ability of choline to produce TMAO was stronger than that of betaine and L-carnitine. Long-term dietary intervention would affect the metabolism of precursors to generate TMA and the TMA oxidation to form TMAO, suggesting that TMAO levels in vivo could be regulated by adjustment of dietary structure.


Assuntos
Betaína/metabolismo , Carnitina/metabolismo , Colina/metabolismo , Metilaminas/sangue , Animais , Feminino , Microbioma Gastrointestinal , Intestinos/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C
17.
Int J Syst Evol Microbiol ; 70(5): 3504-3512, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32416737

RESUMO

A bacteria strain, designated CFH 90008T, was isolated from a salt lake sediment sample collected from Yuncheng city, Shanxi Province, PR China. Strain CFH 90008T was Gram-stain-negative, strictly aerobic, motile with lateral flagella and rod-shaped. Colonies were yellow, circular and smooth. Phylogenetic analyses based on 16S rRNA gene sequences indicated that strain CFH 90008T belonged to the genus Halomonas, showing highest sequence similarity to Halomonas daqingensis DQD2-30T (98.6 %), Halomonas saliphila LCB169T (98.5 %), Halomonas desiderata FB2T (98.1 %) and Halomonas kenyensis AIR-2T (98.0 %). Good growth was observed at 10-50 °C, pH 6.0-9.0 and with NaCl concentration from 1.0 to 12.0 % (w/v). The predominant quinone was Q9. The major fatty acid (>10 %) was C18 : 1 ω7c, C16 : 0 and C16 : 1 ω7c. The genome of strain CFH 90008T was 4.36 Mbp with a genomic DNA G+C content of 66.7 mol%. Based on low average nucleotide identity and DNA-DNAhybridization results, chemotaxonomic characteristics, and differential physiological properties, strain CFH 90008T could not be classified into any recognized species of the genus Halomonas. Therefore, a new species, for which the name Halomonas lactosivorans sp. nov. is proposed. The type strain is CFH 90008T (=DSM 103220T=KCTC 52281T).


Assuntos
Sedimentos Geológicos/microbiologia , Halomonas/classificação , Lagos/microbiologia , Filogenia , Águas Salinas , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/química , Halomonas/isolamento & purificação , Hibridização de Ácido Nucleico , Pigmentação , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/química
18.
Lipids Health Dis ; 19(1): 104, 2020 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-32450867

RESUMO

BACKGROUND: Glycerophospholipids were the main components of cerebral cortex lipids, and there was a close association between lipid homeostasis and human health. It has been reported that dietary DHA-enriched phosphatidylcholine (DHA-PC) and phosphatidylserine (DHA-PS) could improve brain function. However, it was unclear that whether supplementation of DHA-PC and DHA-PS could change lipid profiles in the brain of dementia animals. METHODS: SAMP8 mice was fed with different diet patterns for 2 months, including high-fat diet and low-fat diet. After intervention with DHA-PC and DHA-PS for another 2 months, the lipid profile in cerebral cortex was determined by lipidomics in dementia mice. RESULTS: High-fat diet could significantly decrease the levels of DHA-containing PS/pPE, DPA-containing PS, and AA-containing PE, which might exhibit the potential of lipid biomarkers for the prevention and diagnosis of AD. Notably, DHA-PC and DHA-PS remarkably recovered the lipid homeostasis in dementia mice. These might provide a potential novel therapy strategy and direction of dietary intervention for patients with cognitive decline. CONCLUSIONS: DHA-PC and DHA-PS could recover the content of brain DHA-containing PS and pPE in SAMP8 mice fed with high-fat diet.


Assuntos
Córtex Cerebral/química , Dieta Hiperlipídica , Ácidos Docosa-Hexaenoicos/análise , Fosfatidilcolinas/química , Fosfatidilserinas/análise , Plasmalogênios/análise , Doença de Alzheimer , Animais , Córtex Cerebral/efeitos dos fármacos , Modelos Animais de Doenças , Lipidômica , Masculino , Camundongos , Fosfatidilcolinas/farmacologia , Fosfatidilserinas/química , Fosfatidilserinas/metabolismo , Fosfatidilserinas/farmacologia , Plasmalogênios/química , Plasmalogênios/metabolismo
19.
J Agric Food Chem ; 68(19): 5339-5348, 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32306729

RESUMO

Eicosapentaenoic acid (EPA)-enriched phosphoethanolamine plasmalogens (EPA-PlsEtns) might be retained in the intestine rich in gut microbiota for a long time after treatment. It reminded us that EPA-PlsEtns might affect intestinal microbiota composition and its metabolites, which have been identified as a contributing factor in the development of cardiovascular diseases. In the present study, EPA-PlsEtn administration for 8 weeks significantly reduced the atherosclerotic lesion area in low-density lipoprotein receptor deficient (LDLR-/-) mice. Notably, the serum total cholesterol and low-density lipoprotein cholesterol levels were significantly reduced by 33.6 and 38.2%, respectively, by EPA-PlsEtns instead of EPA in the form of ethyl ester (EPA-EE) treatment compared with the model group. EPA-PlsEtn administration also increased total neutral sterol and bile acids in feces by 92 and 39%, respectively, rather than EPA-EE. Mechanistically, EPA-PlsEtns might affect the abundance of gut microbiota contributing to the alteration of bile acid profiles, which might further accelerate bile acid synthesis via increasing cholesterol 7 α-hydroxylase expression induced by the inhibition of farnesoid X receptor activation.


Assuntos
Aterosclerose/tratamento farmacológico , Ácidos e Sais Biliares/metabolismo , Ácido Eicosapentaenoico/administração & dosagem , Etanolaminas/administração & dosagem , Microbioma Gastrointestinal/efeitos dos fármacos , Plasmalogênios/administração & dosagem , Receptores de LDL/genética , Animais , Aterosclerose/genética , Aterosclerose/metabolismo , Aterosclerose/microbiologia , Colesterol 7-alfa-Hidroxilase/genética , Colesterol 7-alfa-Hidroxilase/metabolismo , Etanolaminas/análise , Humanos , Masculino , Camundongos , Camundongos Knockout , Plasmalogênios/análise , Receptores de LDL/metabolismo
20.
Food Funct ; 11(2): 1441-1454, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-31971532

RESUMO

The beneficial effects of nonpolar DHA/EPA in triacylglycerol (TG) and ethyl ester (EE) forms as well as terrestrial phospholipids on physical fatigue have been widely reported. However, the results involving the effects were inconsistent, and the reason might be that the differences in physical fatigue induced by aerobic and anaerobic exercises were usually ignored. In addition, it has been reported the significant improvement of DHA/EPA esterified to phospholipids (DHA/EPA-PLs) on many fields but not physical fatigue. Therefore, the effects of DHA/EPA-PLs on physical fatigue induced by aerobic and anaerobic exercises were evaluated and compared with those of l-carnitine and astaxanthin using swimming and running exhaustion tests in mice, respectively. The results indicated that DHA/EPA-PLs and l-carnitine have significant effects on the performance of aerobic exercise, while astaxanthin had remarkable effects on the performance of anaerobic exercise. The possible underlying mechanisms indicated that DHA/EPA-PLs significantly promoted the carbohydrate and lipid metabolism as well as the mitochondrial respiratory chain and tricarboxylic acid cycle in muscles. The study presented a potential novel candidate or targeted dietary patterns for alleviating physical fatigue.


Assuntos
Ácidos Docosa-Hexaenoicos/farmacologia , Ácido Eicosapentaenoico/farmacologia , Óleos de Peixe/farmacologia , Atividade Motora/efeitos dos fármacos , Fosfolipídeos/farmacologia , Anaerobiose , Animais , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Projetos Piloto , Pepinos-do-Mar
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