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1.
J Magn Reson Imaging ; 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38100518

RESUMO

BACKGROUND: Extracellular free water (FW) resulting from white matter degeneration limits the sensitivity of diffusion tensor imaging (DTI) in predicting Alzheimer's disease (AD). PURPOSE: To evaluate the sensitivity of FW-DTI in detecting white matter microstructural changes in AD. To validate the effectiveness of FW-DTI indices to predict amyloid-beta (Aß) positivity in mild cognitive impairment (MCI) subtypes. STUDY TYPE: Retrospective. POPULATION: Thirty-eight Aß-negative cognitively healthy (CH) controls (68.74 ± 8.28 years old, 55% female), 15 Aß-negative MCI patients (MCI-n) (68.87 ± 8.83 years old, 60% female), 29 Aß-positive MCI patients (MCI-p) (73.03 ± 7.05 years old, 52% female), and 29 Aß-positive AD patients (72.93 ± 9.11 years old, 55% female). FIELD STRENGTH/SEQUENCE: 3.0T; DTI, T1 -weighted, T2 -weighted, T2 star-weighted angiography, and Aß PET (18 F-florbetaben or 11 C-PIB). ASSESSMENT: FW-corrected and standard diffusion indices were analyzed using trace-based spatial statistics. Area under the curve (AUC) in distinguishing MCI subtypes were compared using support vector machine (SVM). STATISTICAL TESTS: Chi-squared test, one-way analysis of covariance, general linear regression analyses, nonparametric permutation tests, partial Pearson's correlation, receiver operating characteristic curve analysis, and linear SVM. A P value <0.05 was considered statistically significant. RESULTS: Compared with CH/MCI-n/MCI-p, AD showed significant change in tissue compartment indices of FW-DTI. No difference was found in the FW index among pair-wise group comparisons (the minimum FWE-corrected P = 0.114). There was a significant association between FW-DTI indices and memory and visuospatial function. The SVM classifier with tissue radial diffusivity as an input feature had the best classification performance of MCI subtypes (AUC = 0.91), and the classifying accuracy of FW-DTI was all over 89.89%. DATA CONCLUSION: FW-DTI indices prove to be potential biomarkers of AD. The classification of MCI subtypes based on SVM and FW-DTI indices has good accuracy and could help early diagnosis. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

2.
Cogn Process ; 24(2): 173-186, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36708402

RESUMO

To investigate the mechanism of episodic foresight of different valences on intertemporal decision-making, this study examined the mediating role of future self-continuity in the influence of episodic foresight on intertemporal decision-making and the moderating role of perceived control in two experiments. The results found that (1) future self-continuity mediated the effect of episodic foresight on individuals' intertemporal decision-making; and (2) perceived control moderated the indirect effect of episodic foresight on intertemporal decision-making through future self-continuity. Under low perceived control, individuals with positive episodic foresight had stronger future self-continuity and preferred future options, while individuals with negative episodic foresight had lower future self-continuity. In contrast, under high perceived control, individuals with different episodic foresight potencies did not show significant differences in their future self-continuity levels, but all showed higher levels and tended to choose the delayed option when faced with an intertemporal choice. From the perspective of the self-cognition, this study provided new insights into the relationship between episodic foresight and intertemporal decision-making and the psychological mechanisms of intertemporal decision-making.


Assuntos
Desvalorização pelo Atraso , Humanos , Cognição , Imaginação
3.
Eur J Neurosci ; 53(9): 2946-2959, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-32031280

RESUMO

The critical role of mitochondrial dysfunction in the pathological mechanisms of neurodegenerative disorders, particularly Parkinson's disease (PD), is well established. Compelling evidence indicates that Parkinson's proteins (e.g., α-synuclein, Parkin, PINK1, DJ-1, and LRRK2) are associated with mitochondrial dysfunction and oxidative stress in PD. Significantly, there is a possible central role of alpha-synuclein (α-Syn) in the occurrence of mitochondrial dysfunction and oxidative stress by the mediation of different signaling pathways. Also, tau, traditionally considered as the main component of neurofibrillary tangles, aggregates and amplifies the neurotoxic effects on mitochondria by interacting with α-Syn. Moreover, oxidative stress caused by mitochondrial dysfunction favors assembly of both α-Syn and tau and also plays a key role in the formation of protein aggregates. In this review, we provide an overview of the relationship between these two pathological proteins and mitochondrial dysfunction in PD, and also summarize the underlying mechanisms in the interplay of α-Syn aggregation and phosphorylated tau targeting the mitochondria, to find new strategies to prevent PD processing.


Assuntos
Doenças Neurodegenerativas , Doença de Parkinson , Humanos , Mitocôndrias/metabolismo , Doenças Neurodegenerativas/metabolismo , Estresse Oxidativo , Doença de Parkinson/metabolismo , alfa-Sinucleína/metabolismo
4.
J Org Chem ; 86(24): 17975-17985, 2021 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-34860531

RESUMO

Iron-catalyzed oxidative amination of benzylic C(sp3)-H bonds with anilines bearing electron-withdrawing groups (EWGs) or electron-donating groups (EDGs) is realized based on simple variations of N-substituents on imidazolium cations in novel ionic Fe(III) complexes. The structural modification of the imidazolium cation resulted in regulation of the redox potential and the catalytic performance of the iron metal center. Using DTBP as oxidant, [HItBu][FeBr4] showed the highest catalytic activity for anilines bearing EWGs, while [HIPym][FeBr4] was more efficient for EDG-substituted anilines. This work provides alternative access to benzylamines with the advantages of both a wide substrate scope and iron catalysis.

5.
Pharmacol Res ; 151: 104553, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31760107

RESUMO

Parkinson's disease (PD) that afflicts millions of individuals worldwide is associated with deposits of aggregate-prone proteins (e.g., α-synuclein) and with mitochondrial dysfunction in neuronal cells. Mitochondria are the main source of reactive oxygen species, provide energy for neuronal cells, and are regarded as dynamic organelles that are determined by mitochondrial fission, fusion, and mitophagy to maintain mitochondrial homeostasis. Growing evidence reveals that several dynamics-related proteins, such as dynamin-related protein 1 (Drp1), mediate mitochondrial fission, fusion, and mitophagy, to protect against neurodegeneration in PD. More importantly, not only is Drp1-mediated fission required for mitophagy that exerts a protective effect on neurons, but abnormal mitochondrial fission and mitophagy can drive neuronal survival or cell death (i.e., autophagy, apoptosis, and necroptosis), suggesting that Drp1 may play a pivotal role in the pathogenesis of PD. Also, PD-related proteins such as α-synuclein, leucine-rich repeat kinase-2, PTEN-induced putative kinase 1, and Parkin have been proven to interact with Drp1, thus contributing to mitochondrial dynamics and clearance, as well as neuronal fate. Here, we review the roles of Drp1 in mitochondrial fission, dynamics, mitophagy, bulk autophagy, apoptosis, and necroptosis for a better understanding of mitochondrial disturbances in PD-associated neurodegeneration and summarize the advances of novel chemical compounds targeting Drp1 to provide new insight into potential PD therapies.


Assuntos
Dinaminas/metabolismo , Dinâmica Mitocondrial , Mitofagia , Neurônios/patologia , Doença de Parkinson/patologia , Animais , Antiparkinsonianos/farmacologia , Antiparkinsonianos/uso terapêutico , Morte Celular/efeitos dos fármacos , Descoberta de Drogas , Dinaminas/análise , Humanos , Dinâmica Mitocondrial/efeitos dos fármacos , Mitofagia/efeitos dos fármacos , Terapia de Alvo Molecular , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo
6.
Cogn Process ; 21(1): 23-32, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31520168

RESUMO

The similarity of the features between two entities has been assumed to be the essential factor for distinguishing these two entities across a variety of cognitive acts; however, the mechanism underlying the similarity processing remains unclear. The perceptual-based account suggests that similarity judgment is based on perceptual features between entities, whereas other accounts assume that similarity judgment relies heavily on one's previous knowledge of the entities. In Experiment 1, we explored the influence of theoretical knowledge on similarity judgment when perceptual features conflict with conceptual information. In Experiment 2, we examined whether categorization tasks further influence the results of the similarity judgment. Our results showed that the theoretical knowledge contributed to the overall similarity of the stimuli. In addition, carrying out a categorization task or not did not contribute more to the processes of the similarity judgment. Overall, these findings suggest that the conceptual information is more important than perceptual features while judging the similarity of two entities; if sufficient theoretical knowledge is available, the criteria for carrying out the categorization task might be consistent with those for the similarity judgment in the present study.


Assuntos
Julgamento , Conhecimento , Humanos
7.
Pharmacol Res ; 146: 104336, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31271846

RESUMO

Alzheimer's disease (AD) and Parkinson's disease (PD) are recognized as the universal neurodegenerative diseases, with the involvement of misfolded proteins pathology, leading to oxidative stress, glial cells activation, neuroinflammation, mitochondrial dysfunction, and cellular apoptosis. Several discoveries indicate that accumulation of pathogenic proteins, i.e. amyloid ß (Aß), the microtubule-binding protein tau, and α-synuclein, are parallel with oxidative stress, neuroinflammation, and mitochondrial dysfunction. Whether the causative factors are misfolded proteins or these pathophysiological changes, leading to neurodegeneration still remain ambiguous. Importantly, directing pharmacological researches towards the prevention of AD and PD seem a promising approach to detect these complicating mechanisms, and provide new insight into therapy for AD and PD patients. Mangiferin (MGF, 2-C-ß-D-glucopyranosyl-1, 3, 6, 7-tetrahydroxyxanthone), well-known as a natural product, is detached from multiple plants, including Mangifera indica L. With the structure of C-glycosyl and phenolic moiety, MGF possesses multipotent properties starting from anti-oxidant effects, to the alleviation of mitochondrial dysfunction, neuroinflammation, and cellular apoptosis. In particular, MGF can cross the blood-brain barrier to exert neuronal protection. Different researches implicate that MGF is able to protect the central nervous system from oxidative stress, mitochondrial dysfunction, neuroinflammation, and apoptosis under in vitro and in vivo models. Additional facts support that MGF plays a role in improving the declined memory and cognition of rat models. Taken together, the neuroprotective capacity of MGF may stand out as an agent candidate for AD and PD therapy.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Xantonas/farmacologia , Xantonas/uso terapêutico , Animais , Antioxidantes/fisiologia , Antioxidantes/uso terapêutico , Humanos , Estresse Oxidativo/efeitos dos fármacos
8.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 49(6): 876-880, 2018 Nov.
Artigo em Zh | MEDLINE | ID: mdl-32677396

RESUMO

OBJECTIVE: To determine the function of potassium channel in KCNQ2 G271V mutants of benign familial neonatal convulsions. METHODS: HEK293 cells were transfected with pcDNA3-WT-KCNQ2 and / or pcDNA3-G271V-KCNQ2 and pcDNA3-WT-KCNQ3. The potassium channel function of G271V mutants was assessed using the whole cell patch clamp technique. RESULTS: G271V mutants did not show currents in the transfected HEK cells, inducing large depolarizing shift of the conductance voltage relationship and slowing down the current activation kinetics. The required current density was (2.47±0.41) pA/pF (n=12) for the expression of G271V, and whereas (20.53±2.51) pA/pF (n=10,P<0.001) for Kv7.2. G271V mutants abolished currents in the homomeric channel. Kv7.2/Kv7.3 induced robust current was (123.68±15.21) pA/pF (n=15) and Kv7.2/G271V/Kv7.3 (42.71±6.27) pA/pF (n=10), G271V/Kv7.3 induced almost no current (3.74±0.76) pA/pF (n=10,P<0.05), resulting in about 50% reduction of currents in Kv7.2/G271V/Kv7.3 in the heteromultimeric condition. CONCLUSIONS: The G271V channel fails to open potassium currents in response to depolarization, indicating a more severe functional defect of the Kv7 potassium channel.

9.
Zhongguo Zhong Yao Za Zhi ; 43(24): 4842-4849, 2018 Dec.
Artigo em Zh | MEDLINE | ID: mdl-30717529

RESUMO

Selaginella tamariscina is a typical resuscitation medicinal plant with extreme drought tolerance. Trehalose plays an important role in the resurrection process, and the trehalose-6-phosphate synthase(TPS) is the key enzyme to synthesize trehalose in plants. In this study, the sequence of TPS was obtained by splicing from the transcriptome data of S. tamariscina. After the synthesis of cDNA based on the template of total RNA, the sequence was cloned by RT-PCR for verification and then analyzed by bioinformatics methods. The results indicated that the full-length coding sequence of StTPS was 2 799 bp (GenBank accession no. MH155231), and the encoded protein contained 932 amino acids. StTPS could be located in the chloroplastid according to subcellular localization prediction. There were two conserved domains belonging to glycogen phosphorylase glycosyltransferase (GPGTF) family but no signal peptide or transmembrane domain in StTPS. The expression of StTPS was determined by qRT-PCR and the variation of trehalose content was measured by HPLC-ELSD during the resurrection process of S. tamariscina. Meanwhile, the correlation between them was analyzed. The results showed that both the expression level of StTPS and the trehalose content increased associated with the extension of dehydration time, and declined associated with the extension of rehydration time which proved a significant positive correlation between the StTPS expression level and the trehalose content. The results suggested that the StTPS probably plays a central role in recovery process in S. tamariscina.


Assuntos
Selaginellaceae , Sequência de Aminoácidos , DNA Complementar , Glucosiltransferases , Trealose
10.
Biomed Environ Sci ; 30(5): 343-350, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28549490

RESUMO

OBJECTIVE: Mutations in 23S rRNA gene are known to be associated with macrolide resistance in Mycoplasma pneumoniae (M. pneumoniae). However, these mutations alone do not fully explain the high resistance rates in Asia. The aim of this study was to investigate other possible mutations involved in macrolide resistance in M. pneumoniae. METHODS: The whole genomes of 10 clinical isolates of M. pneumoniae with macrolide resistance were sequenced by Illumina HiSeq2000 platform. The role of the macrolide-specific efflux transporter was assessed by efflux-pump inhibition assays with reserpine and carbonyl cyanide m-chlorophenyl-hydrazone (CCCP). RESULTS: A total of 56 single nucleotide polymorphisms (SNPs) were identified in 10 clinical isolates in comparison to the reference strains M129 and FH. Strikingly, 4 of 30 SNPs causing non-synonymous mutations were clustered in macrolide-specific efflux system gene macB encoding macrolide-specific efflux pump protein of the ATP-binding cassette transporter family. In assays of the minimal inhibitory concentrations (MIC) of macrolide antibiotics in the presence of the efflux pump inhibitors caused a significant decrease of MICs, even under detectable levels in some strains. CONCLUSION: Our study suggests that macrolide efflux pump may contribute to macrolide resistance in M. pneumoniae in addition to the common point mutations in 23S rRNA gene.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana/genética , Macrolídeos/farmacologia , Mutação , Mycoplasma pneumoniae/efeitos dos fármacos , Estudo de Associação Genômica Ampla , Testes de Sensibilidade Microbiana , Mycoplasma pneumoniae/genética
11.
Molecules ; 22(9)2017 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-28841191

RESUMO

Natural products from the genus Euphorbia show attention-attracting activities, such as anticancer activity. In this article, classical isolation and structure identification were used in a study on Caper Euphorbia Seed. Subsequently, MTT and wound healing assays, flow cytometry, western blotting, Hoechst 33258 staining and fluorescence microscopy examination were applied to investigate the anticancer activity of the obtained compounds. In a result, lathyrol-3-phenyl- acetate-5,15-diacetate (deoxy Euphorbia factor L1, DEFL1) was isolated from Caper Euphorbia Seed. Moreover, the NMR signals were totally assigned. DEFL1 showed potent inhibition against lung cancer A549 cells, with an IC50 value of 17.51 ± 0.85 µM. Furthermore, DEFL1 suppressed wound healing of A549 cells in a concentration-dependent manner. Mechanically, DEFL1 induced apoptosis, with involvement of an increase of reactive oxygen species (ROS), decrease of mitochondrial membrane potential (ΔΨm), release of cytochrome c, activity raise of caspase-9 and 3. Characteristic features of apoptosis were observed by fluorescence microscopy. In summary, DEFL1 inhibited growth and induced apoptosis in lung cancer A549 cells via a mitochondrial pathway.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Euphorbia/química , Células A549 , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Citocromos c/metabolismo , Células HCT116 , Humanos , Células KB , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/fisiologia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Sementes/química
12.
Eur J Neurosci ; 43(10): 1379-88, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26913805

RESUMO

DJ-1/PARK7, the Parkinson's disease-related protein, plays an important role in mitochondrial function. However, the mechanisms by which DJ-1 affects mitochondrial function are not fully understood. Akt is a promoter of neuron survival and is partly involved in the neurodegenerative process. This research aimed at investigating a possible relationship between DJ-1 and Akt signalling in regulating mitochondrial function in the dopaminergic neuron-like cells SH-SY5Y and PC-12. Overexpression of DJ-1 was firstly validated at both the transcriptional and translational levels after transit transfection with plasmid pcDNA3-Flag-DJ-1. Confocal fluorescence microscopy demonstrated that overexpression of DJ-1 increased the mitochondrial mass, but did not disrupt the mitochondrial morphology. In addition, mitochondrial complex I activity was raised in DJ-1-overexpressing cells, and this rise occurred with an increase in cellular adenosine 5'-triphosphate content. Moreover, immunoblotting demonstrated that the levels of phosphoinositide 3-kinase and the total Akt were not altered in DJ-1-overexpressing cells, and nor was the Akt phosphorylation on serine 473 changed. By contrast, Akt phosphorylation on threonine 308 was significantly augmented by overexpression of DJ-1, and the expression of glycogen synthase kinase-3beta, a downstream effector of Akt, was suppressed. In summary, these results suggest that overexpression of DJ-1 improves the mitochondrial function, at least in part, through a mechanism involving Akt phosphorylation on threonine 308.


Assuntos
Neurônios Dopaminérgicos/metabolismo , Mitocôndrias/metabolismo , Doença de Parkinson/metabolismo , Proteína Desglicase DJ-1/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Linhagem Celular Tumoral , Complexo I de Transporte de Elétrons/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Fosforilação , Ratos , Treonina/metabolismo
13.
Org Biomol Chem ; 14(12): 3314-21, 2016 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-26940697

RESUMO

An efficient one-pot intermolecular reductive cross-coupling of unactivated primary and secondary alkyl chlorides bearing ß-hydrogens with aryl bromides is described. A combination of magnesium turnings and a catalytic amount of the commercially available iron(iii) complex Fe(PPh3)2Cl3 was used, and the conditions were also successfully extended to an intramolecular reaction for the first time. Both types of cross-coupling reactions proceed under mild conditions, involving the in situ generation of aryl Grignard reagents, and show good applicability to a variety of readily available unactivated alkyl chlorides, which have previously been challenging substrates in iron-catalyzed reductive cross-coupling reactions.

14.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 36(4): 476-9, 2016 Apr.
Artigo em Zh | MEDLINE | ID: mdl-27323623

RESUMO

OBJECTIVE: To explore the analgesic mechanism of small knife needle for treating transverse process syndrome of the third vertebra (TPSTV) by observing peripheral and central changesof ß-endorphin (ß-EP) and enkephalin (ENK) contents. METHODS: Totally 30 Japanese white big-ear rabbits of clean grade were divided into 5 groups according to random digit table, i.e., the normal control group, the model group, the small knife needle group, the electroacupunture (EA) group, and the small knife needle plus EA group, 6 in each group. The TPSTV model was established by inserting a piece of gelatin sponge into the left transverse process of 3rd lumbar vertebrae. Rabbits in the small knife needlegroup were intervened by small knife needle. Those in the EA group were intervened by EA at bilateralWeizhong (BL40). Those in the small knife needle plus EA group were intervened by small knife needleand EA at bilateral Weizhong (BL40). Contents of ß-EP and ENK in plasma, muscle, spinal cord, and hypothalamus were determined after sample collection at day 28 after modeling. RESULTS: Compared with the normal control group, contents of ß-EP and ENK in plasma and muscle increased significantly, and contents of ß-EP and ENK in spinal cord and hypothalamus decreased significantly in the model group (P < 0.05, P < 0.01). Contents of ß-EP and ENK approximated normal levels in the three treatment groups after respective treatment. Compared with the model group, the content of ß-EP in muscle decreased, and contents of ß-EP and ENK in hypothalamus increased in the three treatment groups after respective treatment (P < 0.05). There were no significant difference among the three treatment groups (P > 0.05). CONCLUSIONS: Small knife needle treatment and EA had benign regulation on peripheral and central ß-EP and ENK in TPSTV rabbits. Small knife needle treatment showed better effect than that of EA.


Assuntos
Eletroacupuntura , Encefalinas/metabolismo , Vértebras Lombares/patologia , Doenças da Coluna Vertebral/terapia , beta-Endorfina/metabolismo , Pontos de Acupuntura , Animais , Hipotálamo/metabolismo , Músculo Esquelético/metabolismo , Agulhas , Coelhos , Distribuição Aleatória , Medula Espinal/metabolismo
15.
BMC Bioinformatics ; 16: 76, 2015 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-25887648

RESUMO

BACKGROUND: Obesity-induced chronic inflammation plays a fundamental role in the pathogenesis of metabolic syndrome (MS). Recently, a growing body of evidence supports that miRNAs are largely dysregulated in obesity and that specific miRNAs regulate obesity-associated inflammation. We applied an approach aiming to identify active miRNA-TF-gene regulatory pathways in obesity. Firstly, we detected differentially expressed genes (DEGs) and differentially expressed miRNAs (DEmiRs) from mRNA and miRNA expression profiles, respectively. Secondly, by mapping the DEGs and DEmiRs to the curated miRNA-TF-gene regulatory network as active seed nodes and connect them with their immediate neighbors, we obtained the potential active miRNA-TF-gene regulatory subnetwork in obesity. Thirdly, using a Breadth-First-Search (BFS) algorithm, we identified potential active miRNA-TF-gene regulatory pathways in obesity. Finally, through the hypergeometric test, we identified the active miRNA-TF-gene regulatory pathways that were significantly related to obesity. RESULTS: The potential active pathways with FDR < 0.0005 were considered to be the active miRNA-TF regulatory pathways in obesity. The union of the active pathways is visualized and identical nodes of the active pathways were merged. CONCLUSIONS: We identified 23 active miRNA-TF-gene regulatory pathways that were significantly related to obesity-related inflammation.


Assuntos
Algoritmos , Redes Reguladoras de Genes , Inflamação/etiologia , MicroRNAs/genética , Obesidade/complicações , RNA Mensageiro/genética , Fatores de Transcrição/metabolismo , Bases de Dados Factuais , Perfilação da Expressão Gênica , Humanos , MicroRNAs/metabolismo , RNA Mensageiro/metabolismo
16.
J Alzheimers Dis ; 98(2): 373-385, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38461506

RESUMO

Background: Emerging evidence suggests the potential relationship between vitamin D deficiency and risk of cognitive impairment or dementia. To what extent the excess risk of dementia conferred by vitamin D deficiency is less clear. Objective: We summarized the current evidence from several aspects and further quantified these associations. Methods: We collected relevant prospective cohort studies by searching PubMed, Embase and Cochrane up to July 2023. The pooled relative risks (RR) were evaluated by random-effects models. Dose-response analyses were conducted by the method of two-stage generalized least squares regression. Results: Of 9,267 identified literatures, 23 were eligible for inclusion in the meta-analyses, among which 9 and 4 literatures were included in the dose-response analyses for the risk of dementia and Alzheimer's disease (AD). Vitamin D deficiency exhibited a 1.42 times risk for dementia (95% confidence interval (CI) = 1.21-1.65) and a 1.57-fold excess risk for AD (95% CI = 1.15-2.14). And vitamin D deficiency was associated with 34% elevated risk with cognitive impairment (95% CI = 1.19-1.52). Additionally, vitamin D was non-linearly related to the risk of dementia (pnonlinearity = 0.0000) and AD (pnonlinearity = 0.0042). The approximate 77.5-100 nmol/L 25-hydroxyvitamin D [25(OH)D] was optimal for reducing dementia risk. And the AD risk seemed to be decreased when the 25(OH)D level >40.1 nmol/L. Conclusions: Vitamin D deficiency was a risk factor for dementia, AD, and cognitive impairment. The nonlinear relationships may further provide the optimum dose of 25(OH)D for dementia prevention.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Deficiência de Vitamina D , Humanos , Estudos Prospectivos , Vitamina D/uso terapêutico , Doença de Alzheimer/complicações , Disfunção Cognitiva/complicações , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/epidemiologia , Vitaminas/uso terapêutico , Fatores de Risco
18.
Org Biomol Chem ; 11(46): 8135-44, 2013 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-24145602

RESUMO

A novel bis(phenol)-functionalized benzimidazolium salt, 1,3-bis(3,5-di-tert-butyl-2-hydroxybenzyl)benzimidazolium chloride (H3LCl, 1), was designed and used to prepare ionic iron(III) complexes of the type [H3L][FeX4] (X = Cl, 2; X = Br, 3). Both 2 and 3 were characterized by elemental analysis, Raman spectroscopy, electrospray ionization mass spectrometry and X-ray crystallography. The catalytic performances of 2 and 3 in cross-coupling reactions using aryl Grignard reagents with primary and secondary alkyl halides bearing ß-hydrogens were studied. This analysis shows that complex 2 has good potential for alkyl chloride-mediated coupling. In comparison, complex 3 showed slightly lower catalytic activity. After decanting the product contained in the ethereal layer, complex 2 could be recycled at least eight times without significant loss of catalytic activity.

19.
Am J Med Genet B Neuropsychiatr Genet ; 162B(3): 235-44, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23436552

RESUMO

Parkinson's disease (PD) is one of the most common movement disorders. Parkin p.Val380Leu polymorphism (c.1239G > C) has been investigated as a potential genetic hallmark of PD, but studies examining the association between the polymorphism and PD have reported conflicting results. Therefore, we conducted a meta-analysis to assess the influence of Parkin p.Val380Leu polymorphism on the susceptibility of PD. Computer and hand searches of the literature were conducted using the MEDLINE, EMBASE, Cochrane Library, and China Academic Journals databases to identify studies addressing the association between the Parkin p.Val380Leu polymorphism and PD risk. We performed analyses of study characteristics, heterogeneity, and funnel plot asymmetry in analyses analogous to additive, dominant, recessive, homozygous, and heterozygous genetic models with the odds ratio (OR) as the measure of association. A total of 11 case-control studies involving 2,073 PD cases and 2,131 controls were included. When all 11 studies were pooled into the analysis, the presence of the Leu allele at the Parkin p.Val389Leu polymorphism was associated with decreased risk for PD in three genetic comparison models: OR in additive model: 0.79, 95% confidence interval (CI) = 0.64-0.98, P = 0.029; OR in recessive model: 0.55, 95% CI = 0.35-0.89, P = 0.014; OR in homozygous model: 0.51, 95% CI = 0.32-0.82, P = 0.005. Begg's funnel plot and Egger's test provided visual and statistical evidences for funnel plot symmetry, without evidence presence of publication bias. We conclude that the presence of the Leu allele at the Parkin p.Val380Leu polymorphism is associated decreased risk for PD.


Assuntos
Predisposição Genética para Doença , Doença de Parkinson/genética , Ubiquitina-Proteína Ligases/genética , Adulto , Idade de Início , Idoso , Feminino , Estudos de Associação Genética , Genótipo , Heterozigoto , Homozigoto , Humanos , Leucina/genética , Masculino , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo Genético , Valina/genética
20.
Food Sci Nutr ; 11(10): 6096-6105, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37823134

RESUMO

In recent decades, great progress in the area of enteral nutrition has provided a large variety and commercial availability of enteral formulas, usually produced by the nutrition divisions of several pharmaceutical or dairy manufacturers, with specific compositions for each type of disease or patient condition. Despite the widespread use of enteral formulas, both in hospitals and at home, studies performed on the micronutrient compositions of adult enteral formulas are few in China. The content of micronutrients in 31 commercially available adult enteral formulas in the Chinese market was compared with the Chinese dietary reference intakes (DRIs), the tolerable upper limits (UL), the limit requirements in Food Safety National Standards General Rules of Foods for Special Medical Purposes (GB 29922-2013), and the European Society for Clinical Nutrition and Metabolism (ESPEN) micronutrient guideline (2022). The micronutrient content was calculated by multiplying the value provided on the nutrition label for each product by the daily energy dose of 1500 and 1800 Kcal/day. The research results showed that most adult enteral formulas were generally suitable for patients on long-term total enteral nutrition support in the Chinese market, and foods for special medical purpose (FSMP) formulas were more suitable than enteral nutrition preparation (ENP) formulas. However, the vitamin D, vitamin K, and iron content in these formulas should be appropriately increased to the limit recommended by the ESPEN micronutrient guideline. The results could provide a basis for manufacturers to research and develop more suitable enteral formulas and help clinical dietitians administer more effective enteral nutrition support for patients on long-term total enteral nutrition in clinical practice, especially individualized treatment.

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