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1.
J Alzheimers Dis ; 80(1): 271-281, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33523009

RESUMO

BACKGROUND: Identifying modifiable risk factors, such as obesity, to lower the prevalence of Alzheimer's disease (AD) has gained much interest. However, whether the association is causal remains to be evaluated. OBJECTIVE: The present study was designed: 1) to make a quantitative assessment of the association between obesity and AD; 2) to validate whether there was a causal association between them; and 3) to provide genetic clues for the association through a network-based analysis. METHODS: Two-sample Mendelian randomization (2SMR) analysis, meta-analysis, and protein-protein interaction (PPI) network analysis, were employed. RESULTS: Firstly, the meta-analysis based on 9 studies comprising 6,986,436 subjects indicated that midlife obesity had 33%higher AD odds than controls (OR = 1.33, 95%CI = [1.03, 1.62]), while late-life obesity were inversely associated with AD risk (OR = 0.57, 95%CI = [0.47, 0.68]). Secondly, 2SMR analysis indicated that there was no causal association between them. Thirdly, CARTPT was identified to be shared by the anti-obesity drug targets and AD susceptibility genes. Further PPI network analysis found that CARTPT interacted with CD33, a strong genetic locus linked to AD. Finally, 2SMR analysis showed that CNR1 could be a protective factor for AD. CONCLUSION: Multiple bioinformatic analyses indicated that midlife obesity might increase the risk of AD, while current evidence indicated that there was no causal association between them. Further, CARTPT might be an important factor linking the two disease conditions. It could help to better understand the mechanisms underlying the associations between obesity and AD.

2.
PLoS One ; 16(2): e0247248, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33600459

RESUMO

The conversion of cellular prion protein (PrPC) to disease-provoking conformer (PrPSc) is crucial in the pathogenesis of prion diseases. Heparin has been shown to enhance mammalian prion protein misfolding. As spontaneous prion disease has not been reported in non-mammalian species, such as chicken, it is interesting to explore the influence of heparin on the conversion of chicken prion protein (ChPrP). Herein, we investigated the influences of heparin on biochemical properties of full-length recombinant ChPrP, with murine prion protein (MoPrP) as control. The results showed that at low heparin concentration (10 µg/mL), a great loss of solubility was observed for both MoPrP and ChPrP using solubility assays. In contrast, when the concentration of heparin was high (30 µg/mL), the solubility of MoPrP and ChPrP both decreased slightly. Using circular dichroism, PK digestion and transmission electron microscopy, significantly increased ß-sheet content, PK resistance and size of aggregates were observed for MoPrP interacted with 30 µg/mL heparin, whereas 30 µg/mL heparin-treated ChPrP showed less PK resistance and slight increase of ß-sheet structure. Therefore, heparin can induce conformational changes in both MoPrP and ChPrP and the biochemical properties of the aggregates induced by heparin could be modified by heparin concentration. These results highlight the importance of concentration of cofactors affecting PrP misfolding.

3.
Appl Microbiol Biotechnol ; 105(3): 1007-1015, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33449129

RESUMO

Transition metal ions are essential micronutrients for all living organisms and exert a wide range of effects on human health. The uptake of transition metal ions occurs primarily in the gastrointestinal tract, which is colonized by trillions of bacterial cells. In recent years, increasing studies have indicated that transition metals have regulatory effects on the gut microbiota. In view of the significant effect of the gut microbiota on human health and involvement in the pathogenesis of a wide range of diseases, in this paper, we provide a comprehensive discussion on the regulatory effects of four kinds of transition metal ions on the gut microbiota. A total of 20 animal model and human studies concerning the regulatory effects of four types of transition metal ions (i.e., iron, copper, zinc, and manganese) on gut microbiota were summarized. Both the deficiency and supplementation of these transition metal ions on the gut microbiota were considered. Furthermore, the potential mechanisms governing the regulatory effects of transition metal ions on the gut microbiota were also discussed. KEY POINTS : • Regulatory effects of iron, copper, zinc, and manganese on gut microbiota were reviewed. • Both deficiency and supplementation of metal ions on gut microbiota were considered. • Mechanisms governing effects of metal ions on gut microbiota were discussed.

4.
Brief Bioinform ; 2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-32951050

RESUMO

In view of great difficulties in the pathogenesis analysis of Alzheimer's disease (AD) presently, profiling the modifiable risk factors is crucial for early detection and intervention of AD. However, the causal associations among them have yet to be identified, and the effective integration and application of these data also remain considerable challenges due to the lack of efficient collection and analysis procedures. To address this issue, we performed comprehensive analyses by two-sample Mendelian randomization (2SMR) and established the AlzRiskMR database (https://github.com/SDBMC/RiskFactors2AD). Four 2SMR analysis methods, including inverse variance weighted (IVW), MR-Egger, weighted median, and weighted mode, were used for the complementary calculation to test the reliability of the results. The database currently comprises 1870 sets of data of Genome-Wide Association Studies (GWAS) from the MR-Base and NHGRI-EBI GWAS Catalog database. AlzRiskMR database not only estimates causal associations between modifiable risk factors and AD but also offers a useful and timely resource for early intervention of AD development incidence.

5.
Trends Mol Med ; 26(6): 597-614, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32470386

RESUMO

Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) represent two major health burdens with steadily increasing prevalence and accumulating evidence indicates a close relationship between the two disorders. In view of their similar pathogenesis, the potential of T2DM drugs for the treatment of AD has attracted considerable attention in recent years, with inspiring outcomes. Here, we provide a comprehensive overview of the effects of a total of 14 individual drugs (among which are seven T2DM drug types) against AD. Further, we discuss the potential action mechanisms of these T2DM drugs against AD. We argue that these findings may open novel avenues for AD drug discovery, drug target identification, and cotreatment of the two disorders.

6.
Neurobiol Aging ; 91: 167.e11-167.e19, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32204957

RESUMO

With the steadily increasing prevalence of Alzheimer's disease (AD) and great difficulties encountered for AD drug development presently, much interest has been devoted to identifying modifiable risk factors to lower the risk of AD, while the causal associations between risk factors and AD remain inconclusive. The present study conducted a comprehensive evaluation of the causal associations between risk factors and AD development by taking the recent advancements of Mendelian randomization (MR). Inverse variance weighted (IVW), MR-Egger, weighted median, and weighted mode were used for complementary calculation. A total of 45 risk factors and corresponding studies were covered in the study. This two-sample MR (2SMR) analysis provided a suggestive association between genetically predicted higher years of schooling and reduced risks of AD, and each standard deviation (3.71 years) increased in years of schooling was associated with a 41% reduction in the risk of AD (IVW, OR: 0.59, 95% CI: 0.45-0.77). At the same time, it was genetically predicted that urate might be a risk factor in AD, and it was found that each standard deviation increase in urate levels (1.33 mg/dL) was associated with a 0.09-fold increase in the risk of AD (IVW, OR: 1.09, 95% CI: 1.01-1.18). To summarize, the 2SMR analysis indicated a suggestive association between genetically predicted higher years of schooling and reduced risks of AD, and between genetically predicted higher urate levels and increased risks of AD. The findings provide useful clues to help combat AD and warrants future studies.


Assuntos
Doença de Alzheimer/etiologia , Escolaridade , Análise da Randomização Mendeliana/métodos , Ácido Úrico/sangue , Doença de Alzheimer/genética , Estatura , Cobre/sangue , Estudo de Associação Genômica Ampla , Hipocampo/patologia , Humanos , Ácido Linoleico/sangue , Tamanho do Órgão , Polimorfismo de Nucleotídeo Único , Fatores de Risco
7.
Appl Microbiol Biotechnol ; 104(8): 3507-3515, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32095862

RESUMO

Alzheimer's disease (AD) is a neurodegenerative disease with increasing prevalence worldwide, while there are no effective drugs at present. Curcumin, a natural polyphenolic substance isolated from turmeric, is a promising natural compound to combat AD, but its pharmacology remains to be fully understood for its poor in vivo bioavalibility. Inspired by the recently reported associations between gut microbiota and AD development, the present study investigated the interactions of curcumin with gut microbiota of APP/PS1 double transgenic mice from two directions: (i) curcumin influences gut microbiota, and (ii) gut microbiota biotransform curcumin. It was found that curcumin administration tended to improve the spatial learning and memory abilities and reduce the amyloid plaque burden in the hippocampus of APP/PS1 mice. On the one hand, curcumin administration altered significantly the relative abundances of bacterial taxa such as Bacteroidaceae, Prevotellaceae, Lactobacillaceae, and Rikenellaceae at family level, and Prevotella, Bacteroides, and Parabacteroides at genus level, several of which have been reported to be key bacterial species associated with AD development. On the other hand, a total of 8 metabolites of curcumin biotransformed by gut microbiota of AD mice through reduction, demethoxylation, demethylation and hydroxylation were identified by HPLC-Q-TOF/MS, and many of these metabolites have been reported to exhibit neuroprotective ability. The findings provided useful clues to understand the pharmacology of curcumin and microbiome-targeting therapies for AD.

8.
Diabetes Metab Syndr Obes ; 12: 771-778, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31190935

RESUMO

Background: Astragalus possesses therapeutic effects for type 2 diabetes (T2D), while its action mechanisms remain to be elucidated. In view of the pathogenic associations between gut microbiota and T2D, we explored the effect of astragalus on gut-microbiota composition of T2D mice. Materials and methods: Modulation effects of astragalus on gut microbiota of T2D-model mice were assessed by 16S rRNA gene sequencing. Results: Inhibited blood-glucose and body-weight levels of T2D mice by astragalus were accompanied by gut microbiota-composition alteration. Astragalus administration significantly increased gut-microbiota richness and diversity in T2D mice and significantly altered the abundance of several bacterial taxa, inducing increased abundance of Lactobacillus and Bifidobacterium. PICRUSt software revealed the relationship between astragalus and T2D. Conclusion: Due to previously reported decreased gut-microbiota richness and diversity and reduced abundance of key species of Lactobacillus and Bifidobacterium, more studies are encouraged to explore the contribution of gut-microbiota alteration by astragalus to its anti-T2D effect.

9.
Appl Microbiol Biotechnol ; 103(17): 7141-7149, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31236617

RESUMO

The newly reported associations between Alzheimer's disease (AD) and gut microbiota indicate the potential of gut microbiota regulation-based therapeutic intervention for AD. Silymarin and its main active component, silibinin, are promising natural agents against AD, while their acting mechanisms remain to be explored. The present study investigated the effects of silibinin and silymarin administration on behavioral and histological manifestations, and regulation on the gut microbiota of transgenic APP/PS1 mice. First, silibinin and silymarin administration could alleviate memory deficits and reduce the amyloid plaque burden in the brain of APP/PS1 mice in comparison with controls. Second, silibinin and silymarin administration tended to decrease the microbiota diversity and exhibited regulative effect in abundances on several key bacterial species associated with AD development. This implied that gut microbiota regulation by silibinin and silymarin might be involved in their effects against AD. Further studies are warranted to fully elucidate the molecular mechanisms.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Antioxidantes/uso terapêutico , Microbioma Gastrointestinal/efeitos dos fármacos , Silibina/uso terapêutico , Silimarina/uso terapêutico , Doença de Alzheimer/microbiologia , Doença de Alzheimer/patologia , Doença de Alzheimer/psicologia , Animais , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Biodiversidade , Modelos Animais de Doenças , Hipocampo/metabolismo , Aprendizagem/efeitos dos fármacos , Masculino , Camundongos , Camundongos Transgênicos , Placa Amiloide/metabolismo
10.
Food Nutr Res ; 632019.
Artigo em Inglês | MEDLINE | ID: mdl-31205460

RESUMO

Curcuminoids, as the main ingredient of turmeric, are popularly used in food additives and condiments, and are widely accepted to be beneficial for human health for their antioxidant activity. However, curcuminoids are highly susceptible in terms of thermal-induced degradation, and curry is usually boiled, roasted, or fried in the use of food additives and condiments. Thus, it is interesting to explore the effect of cooking on the antioxidant activity of curcuminoids. In the present study, the total antioxidant capacity (T-AOC) of cooked curcuminoids (boiled curcuminoids, roasted curcuminoids, and fried curcuminoids) processed through three heating conditions, and their protective effects against oxidative damage to rat pheochromocytoma (PC12) cells, a well-established neuronal model, were evaluated. It was found that cooking slightly lowered the T-AOC of curcuminoids, with boiled curcuminoids being relatively stronger than roasted curcuminoids, and fried curcuminoids being the weakest form. Both boiled and roasted curcuminoids could significantly improve cell viability, mitigate intracellular accumulation of reactive oxygen species and reduce malondialdehyde activity, reduce caspase-3 and caspase-9 protein expression, and increase superoxide dismutase activity of PC12 cells compared with the control group. In comparison with parent curcuminoids, the protective effects of cooked curcuminoids got relatively lower overall, with boiled curcuminoids being relatively stronger than roasted curcuminoids. In conclusion, the cooked curcuminoids, including boiled and roasted forms, still have antioxidant and neuroprotective activity.

11.
J Alzheimers Dis ; 68(1): 25-31, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30814354

RESUMO

Developing novel agents for unexplored targets to combat Alzheimer's disease (AD) represents an urgent task due to its increasing prevalence worldwide. The present paper summarizes the latest studies emerged in the past few years investigating the associations between the "forgotten organ" gut microbiota and AD from the following two aspects: 1) the associations between gut microbiota and AD development by animal models and human studies; and 2) the effects of gut microbiota modulation-based intervention for AD. Then, we propose future perspectives in two promising research areas: 1) developing gut microbiota modulation-based intervention; and 2) developing gut microbiota-associated diagnostic biomarkers for AD. Knowledge gaps and potential barriers to overcome towards these two goals are also discussed.


Assuntos
Doença de Alzheimer/diagnóstico , Doença de Alzheimer/microbiologia , Microbioma Gastrointestinal/fisiologia , Doença de Alzheimer/terapia , Animais , Modelos Animais de Doenças , Previsões , Trato Gastrointestinal/microbiologia , Trato Gastrointestinal/fisiologia , Humanos
12.
J Neurovirol ; 25(2): 221-228, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30632012

RESUMO

Identifying modifiable risk factors for Parkinson's disease (PD) to help prevent this disease has attracted increasing interest in recent years for the limited effective drugs at present. Despite many studies indicated that infection acts as a risk factor for PD, there is no quantitative assessment of the impact of viral and bacterial infections on the risk of developing PD. The present study performed a meta-analysis on the basis of 38 datasets from 13 studies covering 287,773 PD cases and 7,102,901 controls to ascertain the association between PD and infection and the differences in the strength of the viral and bacterial infections. The overall meta-analytic results indicated that individuals with infection had a 20% increased risk of PD compared with controls (OR 1.20, 95%CI 1.07-1.32). The subgroup analysis according to the type of infection found that bacterial infection had a significant impact on increased risk of PD (OR 1.40, 95%CI 1.32-1.48). The present analysis indicated that infection could increase the risk of developing PD, and physician should be aware of the risk of developing PD in subjects with infection.


Assuntos
Infecções Bacterianas/diagnóstico , Doença de Parkinson/diagnóstico , Viroses/diagnóstico , Infecções Bacterianas/complicações , Infecções Bacterianas/microbiologia , Infecções Bacterianas/virologia , Estudos de Casos e Controles , Helicobacter pylori/patogenicidade , Hepacivirus/patogenicidade , Vírus da Hepatite B/patogenicidade , Herpesvirus Humano 3/patogenicidade , Humanos , Vírus do Sarampo/patogenicidade , Mycobacterium tuberculosis/patogenicidade , Razão de Chances , Orthomyxoviridae/patogenicidade , Doença de Parkinson/complicações , Doença de Parkinson/microbiologia , Doença de Parkinson/virologia , Risco , Simplexvirus/patogenicidade , Streptococcus pyogenes/patogenicidade , Viroses/complicações , Viroses/microbiologia , Viroses/virologia
13.
Crit Rev Food Sci Nutr ; 59(18): 2896-2902, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29781709

RESUMO

Curcumin is a polyphenolic compound with a long history of use as an herbal remedy, dietary spice, and food-coloring agent. Despite curcumin possesses a wide range of biological and pharmacological activities, it exhibits extremely poor bioavailability, which makes its pharmacology intriguing and also hinders its clinical application. In recent years, there is ample evidence supporting the associations between the alteration of gut microbiota and many diseases. Interestingly, after oral administration, curcumin shows its preferential distribution and accumulation in the intestine. In view of the above aspects, we reviewed the updated knowledge regarding the bidirectional interactions between curcumin and gut microbiota from two perspectives: (1) gut microbiota regulation by curcumin and (2) curcumin biotransformation by digestive microbiota. Besides the study deals with 3 potential pharmacological implications: (1) identification of metabolites being more active and bioavaliable than parent curcumin; (2) assessment of contribution of gut microbiota regulation of curcumin to its pharmacological effects and (3) development of gut microbiota regulation-based disease prevention/treatment strategy for curcumin in view of its clinical safety. This review is important to deepen our understanding of the mechanisms of action of curcumin and to provide future directions about how to use this natural compound to combat human diseases.


Assuntos
Curcumina , Microbioma Gastrointestinal , Microbiota , Disponibilidade Biológica , Curcumina/farmacologia , Dieta , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Microbiota/efeitos dos fármacos
14.
Vet Microbiol ; 224: 1-7, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30269782

RESUMO

Prion diseases are characterized by the conformational conversion of the cellular prion protein (PrPC) to the pathogenic isoform (PrPSc). Lipids have been found to interact with PrPC and contribute to the efficient formation of PrPSc. Non-mammalian PrPs are not readily to undergo the conversion process into an infectious isoform, yet the effect of lipid on the conformational conversion of non-mammalian PrPC remains to be explored. Herein, the effects of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG) on full-length recombinant chicken PrP (ChPrP) 24-249 and murine PrP (MoPrP) 23-230 were investigated. Firstly, it was found that in the presence of chemical denaturant, POPG remarkably inhibited MoPrP amyloid fibril growth, while had slight effect on that of ChPrP as estimated by amyloid fibril growth and transmissible electronic microscope assays. Secondly, under physiological condition, POPG induced conformation changes in both MoPrP and ChPrP using Thioflavin T (ThT) fluorescence, circular dichroism, proteinase K digestion and transmission electron microscopy assays. With a POPG:PrP molar ratio of 30:1, the ThT fluorescence of MoPrP was found to be lower than that of ChPrP, however, the POPG-induced MoPrP had higher ß-sheet content and was more proteinase K-resistant than POPG-induced ChPrP. In summary, the present results suggested that the effects of POPG on conformational conversion of MoPrP and ChPrP were different under both denaturation and physiological conditions.


Assuntos
Fosfatidilgliceróis/farmacologia , Proteínas Priônicas/química , Proteínas Priônicas/efeitos dos fármacos , Amiloide/efeitos dos fármacos , Amiloide/fisiologia , Animais , Galinhas , Camundongos , Microscopia Eletrônica de Transmissão , Proteínas Priônicas/genética , Conformação Proteica , Proteínas Recombinantes/efeitos dos fármacos
15.
Food Nutr Res ; 622018.
Artigo em Inglês | MEDLINE | ID: mdl-29942246

RESUMO

Background: As the major active component of turmeric (Curcuma longa), curcumin is widely used as a spice and food coloring agent, and also possesses multiple biological activities and therapeutic potential for neurodegenerative diseases. To answer the paradox between curcumin's biological activities and poor systemic bioavailability, we proposed that degradation products of curcumin may make important contributions to its biological activities, which needs to be verified. In addition, curcumin is usually heated or boiled used as a spice, it is necessary to explore whether boiled curcumin, which degrades readily, is still biologically active. Methods: Thus, in the present study we investigated the protective effects of curcumin and boiled curcumin mixture on H2O2-induced oxidative damage in PC12 cells, a widely used model for neurons. Results: Results showed that in spite of high degradation rates, boiled curcumin mixture still possessed similar protective activities like parent curcumin, and could effectively rescue PC12 cells against H2O2-induced damage, via decreasing production of reactive oxygen species and malondialdehyde, reducing caspase-3 and caspase-9 activities. Moreover, curcumin's degradation products including ferulic acid, vanillin and vanillic acid could also improve PC12 cells survival rate. Conclusion: Our findings indicated that boiled curcumin mixtures still possessed protective activity for PC12 cells, and supported the contribution of degradation products to biological activities of curcumin.

16.
Nutrients ; 10(1)2017 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-29283372

RESUMO

Alzheimer's disease (AD) is the main form of dementia and has a steadily increasing prevalence. As both oxidative stress and metal homeostasis are involved in the pathogenesis of AD, it would be interesting to develop a dual function agent, targeting the two factors. Curcumin, a natural compound isolated from the rhizome of Curcuma longa, is an antioxidant and can also chelate metal ions. Whether the complexes of curcumin with metal ions possess neuroprotective effects has not been evaluated. Therefore, the present study was designed to investigate the protective effects of the complexes of curcumin with Cu(II) or Zn(II) on hydrogen peroxide (H2O2)-induced injury and the underlying molecular mechanisms. The use of rat pheochromocytoma (PC12) cells, a widely used neuronal cell model system, was adopted. It was revealed that curcumin-Cu(II) complexes systems possessed enhanced O2·--scavenging activities compared to unchelated curcumin. In comparison with unchelated curcumin, the protective effects of curcumin-Cu(II) complexes systems were stronger than curcumin-Zn(II) system. Curcumin-Cu(II) or -Zn(II) complexes systems significantly enhanced the superoxide dismutase, catalase, and glutathione peroxidase activities and attenuated the increase of malondialdehyde levels and caspase-3 and caspase-9 activities, in a dose-dependent manner. The curcumin-Cu(II) complex system with a 2:1 ratio exhibited the most significant effect. Further mechanistic study demonstrated that curcumin-Cu(II) or -Zn(II) complexes systems inhibited cell apoptosis via downregulating the nuclear factor κB (NF-κB) pathway and upregulating Bcl-2/Bax pathway. In summary, the present study found that curcumin-Cu(II) or -Zn(II) complexes systems, especially the former, possess significant neuroprotective effects, which indicates the potential advantage of curcumin as a promising agent against AD and deserves further study.


Assuntos
Antioxidantes/farmacologia , Cobre/química , Curcumina/farmacologia , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Zinco/química , Animais , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Catalase/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Curcumina/análogos & derivados , Citoproteção , Relação Dose-Resposta a Droga , Glutationa Peroxidase/metabolismo , Peróxido de Hidrogênio/toxicidade , Malondialdeído/metabolismo , NF-kappa B/metabolismo , Neurônios/metabolismo , Neurônios/patologia , Células PC12 , Ratos , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo
17.
Oncotarget ; 8(34): 55915-55919, 2017 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-28915562

RESUMO

Alzheimer's disease (AD) represents the major form of dementia in the elderly. In recent years, accumulating evidence indicate that obesity may act as a risk factor for AD, while the genetic link between the two conditions remains unclear. This bioinformatics analysis aimed to detect the genetic link between AD and obesity on single nucleotide polymorphisms (SNPs), gene, and pathway levels based on genome-wide association studies data. A total of 31 SNPs were found to be shared by AD and obesity, which were linked to 7 genes. These genes included PSMC3, CELF1, MYBPC3, SPI1, APOE, MTCH2 and RAPSN. Further functional enrichment analysis of these genes revealed the following biological pathways, including proteasome, osteoclast differentiation, hypertrophic cardiomyopathy, dilated cardiomyopathy, Epstein-Barr virus and TLV-I infection, as well as several cancer associated pathways, to be common among AD and obesity. The findings deepened our understanding on the genetic basis linking obesity and AD and may help shape possible prevention and treatment strategies.

18.
Food Nutr Res ; 61(1): 1361780, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28814952

RESUMO

Curcumin, the major active component of turmeric (Curcuma longa), is widely used as a spice and food-coloring agent, and also exhibits multiple biological activities. However, as curcumin has poor systemic bioavailability its pharmacology remains to be elucidated. Owing to the high concentration of curcumin in the gastrointestinal tract after oral administration, we hypothesize that it may exert regulative effects on the gut microbiota. We investigated the regulative effects of oral curcumin administration on the gut microbiota of C57BL/6 mice and found that curcumin significantly affected the abundance of several representative families in gut microbial communities, including Prevotellaceae, Bacteroidaceae, and Rikenellaceae. Considering the pathogenic associations between gut microbiota and many diseases, the present findings may help us to interpret the therapeutic benefits of curcumin.

19.
Oncotarget ; 8(14): 23389-23400, 2017 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-28177893

RESUMO

Diabetes and depression impose an enormous public health burden and the present study aimed to assess quantitatively the bidirectional relationships between the two disorders. We searched databases for eligible articles published until October 2016. A total of 51 studies were finally included in the present bidirectional meta-analysis, among which, 32 studies were about the direction of depression leading to diabetes, and 24 studies about the direction of diabetes leading to depression. Pooled results of the 32 eligible studies covering 1274337 subjects showed that depression patients were at higher risk for diabetes (odds ratio (OR) = 1.34, 95% confidence intervals (CI) = [1.23, 1.46]) than non-depressive subjects. Further gender-subgroup analysis found that the strength of this relationship was stronger in men (OR = 1.63, 95%CI = [1.48, 1.78]) than in women (OR = 1.29, 95%CI = [1.07, 1.51]). For the direction of diabetes leading to depression, pooled data of 24 articles containing 329658 subjects showed that patients with diabetes were at higher risk for diabetes (OR = 1.28, 95%CI = [1.15, 1.42]) than non-diabetic subjects. The available data supports that the relationships between diabetes and depression are bidirectional and the overall strengths are similar in both directions. More mechanistic studies are encouraged to explore the molecular mechanisms underlying the relationships between the two diseases.


Assuntos
Depressão/metabolismo , Diabetes Mellitus Tipo 2/psicologia , Adulto , Idoso , Comorbidade , Depressão/patologia , Diabetes Mellitus Tipo 2/patologia , Estudos de Avaliação como Assunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
20.
J Alzheimers Dis ; 56(1): 385-390, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27911317

RESUMO

Alzheimer's disease (AD) is a neurodegenerative brain disease and is the most common form of dementia. In recent years, many studies indicated the association of gut microbiota changes with metabolic diseases. However, the gut microbiota of AD has not been investigated. The present study aims to compare the gut microbiota in APP/PS1 transgenic mice of AD and C57/Bl6 wild-type (WT) mice by pyrosequencing the V3 and V4 regions of the bacterial 16S ribosomal RNA genes. The 3-, 6-, and 8-month-old APP/PS1 and WT mice were used to explore the effects of age on the gut microbiota. First, the results indicated that impaired spatial learning and memory appeared in 6-month-old APP/PS1 mice and was further aggravated in the 8-month-old group, which was consistent with immunohistochemical studies of amyloid plaque. Second, AD histological and behavioral manifestations in the APP/PS1 mice were found to be correlated with a specific gut microbiome state. Third, the microbiota diversity of APP/PS1 mice decreased with increased age. Fourth, further inspection showed that the abundance of Helicobacteraceae and Desulfovibrionaceae at the family level and Odoribacter and Helicobacter at the genus level increased significantly in APP/PS1 mice than in WT mice, while Prevotella abundance in WT mice was significantly higher than in APP/PS1 mice. More human studies are warranted to explore the potential of gut microbiota as diagnostic biomarkers or therapeutic target for AD.


Assuntos
Doença de Alzheimer/complicações , Sintomas Comportamentais/etiologia , Microbioma Gastrointestinal/fisiologia , Fatores Etários , Doença de Alzheimer/genética , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Análise de Variância , Animais , Modelos Animais de Doenças , Humanos , Aprendizagem em Labirinto/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Fragmentos de Peptídeos/metabolismo , Presenilina-1/genética , RNA Ribossômico 16S/metabolismo
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