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1.
Opt Express ; 26(23): 29956-29967, 2018 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-30469877

RESUMO

The excitation of localized surface plasmon at the metal nanoparticles can significantly enhance the absorption of solar energy. However, the absorption peak is sharp at the resonant frequency. To achieve a broadband absorption, the blended nanofluid formed by SiO2/Ag nanoshells of different core size and shell thickness is employed. The blended nanofluid has a good solar absorption property, whose extinction spectrum matches the solar spectrum well. The transient temperature response of the nanofluid is simulated. It is found that the photothermal performance of the solar thermal collector is related to the geometric parameters and operation conditions of the solar collector, and the optical and thermophysical properties of nanofluid. As the flow velocity increases, the outlet temperature is gradually reduced. But, the collector efficiency is increased since less heat is lost to the environment via convection as nanofluid flows fast in the channel. In order to obtain a large outlet temperature at high velocity, it can be considered to elongate the channel length. Due to the strong extinction properties of the blended nanofluid, the required volume fraction can be significantly reduced, only 1/10 of that of Ag nanofluid for an equal temperature increases.

2.
Chin J Physiol ; 60(6): 313-319, 2017 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-29241304

RESUMO

The diurnal rhythm is the common event in nature and specially shows in the behavioral patterns. Using the infrared sensor or photo beam detector to detect this 24-h rhythmicity in behaviors of mammalian, including in the rats and mice, is also the common way. The photo-sensory detecting mean is friendly and its advantage is unrestricted by light density and light-dark transition. However, this kind of equipment is cost-expensive and uneasy to fit for home cage in rodents. In this study, we tried to use the video-tracking system to detect the rhythmic activity of rats in their home cages. Adult male Sprague-Dawley rats, weighing 250-280 g, were used in this study and individual was kept in its own cage. Combined with the infrared sensitive charge-coupled device (CCD) camera and with automatically lights-off sensitive infrared illuminants as the accessory device, we found that animals exhibited the circadian locomotor activity in either light-dark cycles or constant darkness conditions. Moreover, the rhythmic patterns of locomotion in animals were affected by the one-hour exposure of white light under the constant darkness condition. The phase-advanced effects were found by the video tracking system. In summary, the video tracking system is the useful way to detect the rhythmic activity, especially in long-term circadian rhythmicity, in rats.


Assuntos
Comportamento Animal , Ritmo Circadiano , Gravação em Vídeo/instrumentação , Animais , Masculino , Atividade Motora , Ratos , Ratos Sprague-Dawley
3.
Neurol Neurochir Pol ; 49(4): 290-4, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26188947

RESUMO

Thrombolytic treatment with intravenous recombinant tissue plasminogen activator (rtPA) is an effective treatment for acute ischemic stroke. However, its effectiveness and risks in patients with hypothyroidism have not been reported. Here, we report the case of hemorrhagic transformation after intravenous rtPA thrombolysis treatment in a patient with acute ischemic stroke and hypothyroidism. An apparent edema formed around the hematoma and progressively worsened. He also developed lung infection, electrolyte imbalance, and abnormal liver and kidney functions, and eventually died within 1 month of symptom onset. Thus, our observations suggest that caution should be exercised for the administration of intravenous rtPA thrombolysis to patients with hypothyroidism.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Hemorragia Cerebral/induzido quimicamente , Hipotireoidismo , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica/efeitos adversos , Ativador de Plasminogênio Tecidual/efeitos adversos , Evolução Fatal , Humanos , Masculino , Pessoa de Meia-Idade
4.
Comput Methods Programs Biomed ; 254: 108297, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38905990

RESUMO

BACKGROUND: Parkinson's disease (PD) is a common neurodegenerative disease. Transcranial magnetoacoustic stimulation (TMAS) is a new therapy that combines a transcranial focused acoustic pressure field with a magnetic field to excite or inhibit neurons in targeted area, which suppresses the abnormally elevated beta band amplitude in PD states, with high spatial resolution and non-invasively. OBJECTIVE: To study the effective stimulation parameters of TMAS mononuclear and multinuclear stimulation for the treatment of PD with reduced beta band energy, improved abnormal synchronization, and no thermal damage. METHODS: The TMAS model is constructed based on the volunteer's computed tomography, 128 arrays of phase-controlled transducers, and permanent magnets. A basal ganglia-thalamic (BG-Th) neural network model of the PD state was constructed on the basis of the Izhikevich model and the acoustic model. An ultrasound stimulation neuron model is constructed based on the Hodgkin-Huxley model. Numerical simulations of transcranial focused acoustic pressure field, temperature field and induced electric field at single and dual targets were performed using the locations of STN, GPi, and GPe in the human brain as the main stimulation target areas. And the acoustic and electric parameters at the focus were extracted to stimulate mononuclear and multinuclear in the BG-Th neural network. RESULTS: When the stimulating effect of ultrasound is ignored, TMAS-STN simultaneously inhibits the beta-band amplitude of the GPi nucleus, whereas TMAS-GPi fails to simultaneously have an inhibitory effect on the STN. TMAS-STN&GPi can reduce the beta band amplitude. TMAS-STN&GPi&GPe suppressed the PD pathologic beta band amplitude of each nucleus to a greater extent. When considering the stimulatory effect of ultrasound, lower sound pressures of ultrasound do not affect the neuronal firing state, but higher sound pressures may promote or inhibit the stimulatory effect of induced currents. CONCLUSIONS: At 9 T static magnetic field, 0.5-1.5 MPa and 1.5-2.0 MPa ultrasound had synergistic effects on individual STN and GPi neurons. TMAS multinuclear stimulation with appropriate ultrasound intensity was the most effective in suppressing the amplitude of pathological beta oscillations in PD and may be clinically useful.

5.
Artigo em Inglês | MEDLINE | ID: mdl-38781887

RESUMO

The bay scallop is a eurythermal species with high economic value and now represents the most cultured bivalve species in China. Two subspecies of the bay scallop, the northern subspecies Argopecten irradians irradians Korean population (KK) and the southern subspecies Argopecten irradians concentricus (MM), exhibited distinct adaptations to heat stress. However, the molecular mechanism of heat resistance of the two subspecies remains unclear. In this study, we compared the transcriptomic responses of the two subspecies to heat stress and identified the involved differentially expressed genes (DEGs) and pathways. More DEGs were found in the KK than in the MM when exposed to high temperatures, indicating elevated sensitivity to thermal stress in the KK. Enrichment analysis suggests that KK scallops may respond to heat stress more swiftly by regulating GTPase activity. Meanwhile, MM scallops exhibited higher resistance to heat stress mainly by effective activation of their antioxidant system. Chaperone proteins may play different roles in responses to heat stress in the two subspecies. In both subspecies, the expression levels of antioxidants such as GST were significantly increased; the glycolysis process regulated by PC and PCK1 was greatly intensified; and both apoptotic and anti-apoptotic systems were significantly activated. The pathways related to protein translation and hydrolysis, oxidoreductase activity, organic acid metabolism, and cell apoptosis may also play pivotal roles in the responses to heat stress. The results of this study may provide a theoretical basis for marker-assisted breeding of heat-resistant strains.


Assuntos
Perfilação da Expressão Gênica , Pectinidae , Transcriptoma , Animais , Pectinidae/genética , Pectinidae/fisiologia , Termotolerância/genética , Resposta ao Choque Térmico
6.
Neural Regen Res ; 19(8): 1781-1788, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38103245

RESUMO

JOURNAL/nrgr/04.03/01300535-202408000-00032/figure1/v/2023-12-16T180322Z/r/image-tiff Over the past decade, a growing number of studies have reported transcription factor-based in situ reprogramming that can directly convert endogenous glial cells into functional neurons as an alternative approach for neuroregeneration in the adult mammalian central nervous system. However, many questions remain regarding how a terminally differentiated glial cell can transform into a delicate neuron that forms part of the intricate brain circuitry. In addition, concerns have recently been raised around the absence of astrocyte-to-neuron conversion in astrocytic lineage-tracing mice. In this study, we employed repetitive two-photon imaging to continuously capture the in situ astrocyte-to-neuron conversion process following ectopic expression of the neural transcription factor NeuroD1 in both proliferating reactive astrocytes and lineage-traced astrocytes in the mouse cortex. Time-lapse imaging over several weeks revealed the step-by-step transition from a typical astrocyte with numerous short, tapered branches to a typical neuron with a few long neurites and dynamic growth cones that actively explored the local environment. In addition, these lineage-converting cells were able to migrate radially or tangentially to relocate to suitable positions. Furthermore, two-photon Ca2+ imaging and patch-clamp recordings confirmed that the newly generated neurons exhibited synchronous calcium signals, repetitive action potentials, and spontaneous synaptic responses, suggesting that they had made functional synaptic connections within local neural circuits. In conclusion, we directly visualized the step-by-step lineage conversion process from astrocytes to functional neurons in vivo and unambiguously demonstrated that adult mammalian brains are highly plastic with respect to their potential for neuroregeneration and neural circuit reconstruction.

7.
Alzheimers Res Ther ; 16(1): 22, 2024 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-38281031

RESUMO

BACKGROUND: Alzheimer's disease (AD) is one of the most burdening diseases of the century with no disease-modifying treatment at this time. Nonhuman primates (NHPs) share genetic, anatomical, and physiological similarities with humans, making them ideal model animals for investigating the pathogenesis of AD and potential therapies. However, the use of NHPs in AD research has been hindered by the paucity of AD monkey models due to their long generation time, ethical considerations, and technical challenges in genetically modifying monkeys. METHODS: Here, we developed an AD-like NHP model by overexpressing human tau in the bilateral hippocampi of adult rhesus macaque monkeys. We evaluated the pathological features of these monkeys with immunostaining, Nissl staining, cerebrospinal fluid (CSF) analysis, magnetic resonance imaging (MRI), positron emission tomography (PET), and behavioural tests. RESULTS: We demonstrated that after hippocampal overexpression of tau protein, these monkeys displayed multiple pathological features of AD, including 3-repeat (3R)/4-repeat (4R) tau accumulation, tau hyperphosphorylation, tau propagation, neuronal loss, hippocampal atrophy, neuroinflammation, Aß clearance deficits, blood vessel damage, and cognitive decline. More interestingly, the accumulation of both 3R and 4R tau is specific to NHPs but not found in adult rodents. CONCLUSIONS: This work establishes a tau-induced AD-like NHP model with many key pathological and behavioural features of AD. In addition, our model may potentially become one of the AD NHP models adopted by researchers worldwide since it can be generated within 2 ~ 3 months through a single injection of AAVs into the monkey brains. Hence, our model NHPs may facilitate mechanistic studies and therapeutic treatments for AD.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Animais , Doença de Alzheimer/genética , Proteínas tau/metabolismo , Macaca mulatta/metabolismo , Disfunção Cognitiva/patologia , Hipocampo/patologia , Peptídeos beta-Amiloides/metabolismo
8.
Animals (Basel) ; 13(24)2023 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-38136838

RESUMO

To investigate the shifts in the biochemical composition of hybrid grouper during the early larval stages, we collected samples at various developmental milestones, spanning from newly hatched larvae (stage I) to 4 days after hatching (stage V). Our findings revealed several notable trends: (1) The total length of hybrid grouper larvae exhibited a significant increase as the yolk-sac absorption progressed from stage I to V. Concurrently, there was a marked decrease in yolk volume and oil volume during the transition from stage I to III, followed by a gradual decline from stage III to V. (2) Dry weight and total lipid content displayed a rapid reduction throughout the larval development period, while the total protein content exhibited a declining trend. (3) The concentrations of triacylglycerols and wax esters/steryl esters decreased considerably, particularly at stage V. However, no differences were observed among the contents of ketones, hydrocarbons, and sterols. (4) As yolk-sac larvae developed from stage I to V, a significant reduction was observed in the levels of essential amino acids (EAAs), such as leucine, valine, isoleucine, phenylalanine, glycine, alanine, serine, proline, and tyrosine. This trend was also observed for non-EAAs and total amino acids, with fluctuations in the content of other amino acids. (5) There was a significant decrease in the levels of specific fatty acids, including C16:0, saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), C18:0, 18:1n-9, and C20:4n-6. In contrast, the contents of C22:6n-3, polyunsaturated fatty acids (PUFAs), n-3 PUFA, n-6 PUFA, and the combination of docosahexaenoic acid (DHA) + eicosapentaenoic acid (EPA), as well as the DHA/EPA ratio, remained stable from stage I to III but declined thereafter. (6) During the early developmental stages, the utilization sequence of fatty acids followed a pattern of prioritizing SFAs, followed by MUFAs, n-6 PUFA, and n-3 PUFA. These findings provide further insights into the nutritional priorities of hybrid grouper larvae during their early development, with a particular emphasis on lipids and fatty acids as vital energy sources. Additionally, our results highlight variations in the efficiency of utilization among different types of fatty acids, while protein utilization remained relatively stable, characterized by the selective consumption of amino acid content.

9.
Parkinsonism Relat Disord ; 116: 105890, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37839276

RESUMO

BACKGROUND: Parkinson's disease (PD) is associated with peripheral inflammation and abnormal peripheral blood lymphocyte immune responses. Peripheral blood B-lymphocyte subset distributions and whether they are associated with PD are unclear. METHODS: Sixty-one PD patients and sixty-one one-to-one paired healthy controls (HCs) were enrolled. We used flow cytometry to perform immunophenotyping of peripheral B-lymphocyte, in vitro stimulation and measured serum cytokine. The relationship between variables and PD were assessed. RESULTS: The percentage of naive B cells in blood of PD patients was decreased, whereas the percentages of regulatory B cells (Bregs), plasma blast cells (PBCs), and double-negative (DN) B cells were increased. The absolute counts of B-lymphocyte and naive B cells in blood of PD patients were decreased. Regression analysis revealed that alterations in the absolute counts of B-lymphocyte and the percentage of Bregs and DN B cells were associated with PD. After stimulation, the percentages of Bregs, PBCs, and switched memory (SwM) B cells increased in PD patients. Additionally, increases in GM-CSF-producing B-cell, IFN-γ-producing B-cell, and TNF-α-producing B-cell percentages were noted in PD. Serum levels of a proliferation-inducing ligand (APRIL), B-cell activating factor (BAFF) and soluble CD40 ligand (sCD40L) were elevated in PD and correlated negatively with the UPDRS III score. CONCLUSIONS: Abnormal B-lymphocyte immune responses in peripheral blood may contribute to PD development. Alterations in the absolute counts of B-lymphocyte and the percentage of Bregs and DN B cells are associated with PD. Furthermore, APRIL, BAFF, and sCD40L could be potential targets for intervention in PD.


Assuntos
Linfócitos B Reguladores , Doença de Parkinson , Humanos , Citocinas , Inflamação , Imunidade
10.
Front Neurosci ; 16: 995775, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36408420

RESUMO

Background: Disturbances in circadian rhythms are common among night-shift workers and result in poor sleep quality. Nevertheless, the heterogeneity of circadian rhythms and their relationship with sleep quality is less explored in nursing interns. Therefore, we aimed to identify the latent subtypes of circadian rhythm, explore their relationship with sleep quality, and evaluate their moderating role between perceived stress and sleep quality in nursing interns. Materials and methods: In all, 452 nursing interns were recruited between October 2020 and January 2021 from Be Resilient to Nursing Career (BRNC), which is a multicenter, prospective cohort of a career growth program for nursing students. They were assessed using the 10-item Chinese Perceived Stress Scale, Circadian Type Inventory, and Pittsburgh Sleep Quality Index. Latent profile analysis and moderation analysis were performed. Results: Overall, 72.3% of the nursing interns reported poor sleep quality. We identified three latent subtypes of circadian rhythms, namely, Vigorousness (40.1%), Inadaptability (18.6%), and Flexibility (41.1%). Females (OR = 1.97, 95% Cl: 1.01-3.83, P = 0.047) with normal body mass index (OR = 1.62, 95% CI: 0.95-2.76, P = 0.078) were prone to Flexibility. Circadian rhythm types significantly moderated the association between perceived stress and sleep quality (P < 0.05). Conclusion: Nursing interns suffer from poor sleep. There exists heterogeneity of circadian rhythm subtypes in nursing interns, and attention should be paid to those with Inadaptability type. The association between perceived stress and sleep quality is significantly moderated by circadian rhythm subtypes.

11.
Waste Manag ; 126: 331-339, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33798821

RESUMO

The coexistence of plastics and microalgae in the ocean has brought great challenges to the environment. Therefore, co-pyrolysis of microalgae Dunaliella salina (DS) and typical plastics (polypropylene (PP), polystyrene (PS), polyethylene terephthalate (PET), and polyvinyl chloride (PVC)) were investigated using thermogravimetric analyzer with Fourier transform infrared spectrometer. The results showed that the coating effect of the molten plastics promoted the pyrolysis of DS. The solid residue amounts of DS-PP, DS-PS, and DS-PET blends were reduced by 1.55 wt%, 1.39 wt%, 1.69 wt%, respectively, as a result of the hydrogenation reaction between the unsaturated products generated by plastics and biochar. While for DS-PVC, attributed to the physical and chemical effects during the co-pyrolysis process, the solid residue was increased by 1.36 wt%. For the other three blends, the solid residues were reduced due to the hydrogenation reaction between the unsaturated products generated by plastics and biochar. FTIR analysis of gaseous products indicated the total CO2 production increased significantly for DS-PET. Besides, the alkyls generated by DS reacted with HCl during DS-PVC co-pyrolysis, the resulting products were then fixed in biochar. Kinetic results suggested that due to the co-pyrolysis with DS, the activation energies of PP, PS, and PET were reduced by 1/2, 1/3, and 3/4, respectively, and this value for PVC in its second stage was reduced by 1/4. Our results indicated the advantage to co-pyrolyze the microalgae and marine plastics.


Assuntos
Microalgas , Plásticos , Cinética , Poliestirenos , Pirólise
12.
Bioresour Technol ; 307: 123243, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32244077

RESUMO

The co-pyrolysis behavior of plastic (PP) with six biomass components (cellulose, hemicellulose, lignin, carbohydrate, lipid, protein) was studied by thermogravimetry. The overlap ratio (OR) and the difference in experimental and theoretical weight loss (ΔW) are defined. The results demonstrated that the interaction of lignin and PP was notable with the OR of 0.9661. From ΔW, it was found that the number of solid residues of hemicellulose-PP and lignin-PP decreased by 1.10% and 2.60%, respectively, which was caused by the hydrogenation reaction between the monomers generated by PP and biochar. The DTG peak shift in co-pyrolysis was further studied. By blending with the biomass, the pyrolysis peaks of PP shifted to the high-temperature region and the value was positively correlated with the fixed carbon content in the biomass components. Kinetic analysis revealed that by co-pyrolysis with biomass, the activation energy of the PP decomposition could be reduced by 39.51% -62.71%.


Assuntos
Polipropilenos , Pirólise , Biomassa , Cinética , Lignina , Termogravimetria
13.
Environ Technol ; 41(22): 2898-2906, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30865557

RESUMO

A novel two-stage fluidized-bed/fixed-bed catalytic system was developed for the treatment of benzaldehyde residue. The effects of reaction temperature, oxygen concentration, space velocity on the purification of benzaldehyde production residue were investigated. The effluent chemical oxygen demand (COD) was less than 70 mgO2/L and the COD removal efficiency was higher than 99.83% under our experimental condition (fluidized-bed and fixed-bed temperature of 300-400°C, the flow rate of residue of 10 mL/h and O2 excessive rate of 20). The volatile organic compounds (VOCs) of the outlet were not detected after the treatment. The high-efficiency performance of the process can last for at least 600 h in the stability experiment. It was also verified by gas chromatography-mass spectrometry (GC-MS) analysis that most organic pollutants in the residue were significantly removed after treatment. These results suggest that the two-stage fluidized-bed/fixed-bed catalytic system could be a promising technology for the dispose of chlorine-containing polymer organics in the chemical industry.


Assuntos
Benzaldeídos , Reatores Biológicos , Análise da Demanda Biológica de Oxigênio , Catálise , Temperatura , Eliminação de Resíduos Líquidos
14.
J Nat Prod ; 72(5): 969-72, 2009 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-19374435

RESUMO

Three new norsesquiterpenoid glycosides, 4'-hydroxyphyllaemblicin B (1) and phyllaemblicins E (2) and F (3), were isolated from the roots of Phyllanthus emblica, together with three known compounds, phyllaemblic acid (4), phyllaemblicin B (5), and phyllaemblicin C (6). Of these, 3 is a new norsesquiterpenoid dimer. The structures of 1-3 were established by spectroscopic data information and by acidic hydrolysis. The isolated compounds, together with two other known analogues, phyllaemblic acid methyl ester (7) and phyllaemblicin A (8), were evaluated for their antiviral activity toward coxsackie virus B3 (CVB3) by an in vitro cytopathic effect inhibitory assay. Compounds 5-7 exhibited strong anti-CVB3 activity.


Assuntos
Antivirais/isolamento & purificação , Antivirais/farmacologia , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Enterovirus Humano B/efeitos dos fármacos , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Phyllanthus emblica/química , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacologia , Antivirais/química , Medicamentos de Ervas Chinesas/química , Glicosídeos/química , Células HeLa , Humanos , Estrutura Molecular , Raízes de Plantas/química , Sesquiterpenos/química
15.
Bioresour Technol ; 292: 121970, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31421590

RESUMO

Co-pyrolysis of tobacco stalk (TS) with different types of polymer wastes such as scrap tire (ST), polypropylene (PP) and polyvinyl chloride (PVC) was investigated. Thermogravimetric analyzer coupled with Fourier transform infrared spectrometer was carried out to examine the thermochemical properties, kinetics, and gas generation. The results of the co-pyrolysis showed a synergistic effect compared to the pyrolysis of the individual components. When using TS/ST co-pyrolysis, the reduction in char residue was about 6% (dry wt. basis) and the increase in organic gases exceeded 20%. It indicates that the addition of ST can increase both carbon conversion efficiency and volatiles yield. HCl from PVC underwent a complex physicochemical reaction with TS, increasing coke yield by 11-12% and inhibiting the gas release. In the main pyrolysis temperature range of ST, the activation energy is reduced by 40-80% by blending with TS; for PP this value is reduced by about 22%.


Assuntos
Nicotiana , Polímeros , Gases , Cinética , Pirólise , Termogravimetria
16.
Zhonghua Yi Xue Za Zhi ; 88(17): 1185-8, 2008 Apr 29.
Artigo em Zh | MEDLINE | ID: mdl-18844113

RESUMO

OBJECTIVE: To investigate the association between two estrogen receptor (ER) beta gene polymorphisms and Parkinson disease (PD) as well as Parkinson disease with dementia (PDD) in Chinese people. METHODS: Peripheral blood samples were collected from 115 PD patients (including 26 PDD cases), 56 males and 55 females, aged 64 +/- 10, and 116 sex and age-matched healthy controls. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to analyze the polymorphism of the fifth exon RsaI and the eighth exon AluI of ERbeta gene. Te relationship between each genotype or allele frequencies and PD/PDD was analyzed using chi-square test. RESULTS: There was no difference in the polymorphism of ERbeta genes AluI and Rsa I between the PD group and control group and between the PDD group and control group (all P > 0.05). CONCLUSION: Genetic variations from AluI and RsaI digestion in ERbeta gene do not affect the risk of PD and PDD.


Assuntos
Receptor beta de Estrogênio/genética , Doença de Parkinson/genética , Polimorfismo Genético , Idoso , Sequência de Bases , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição
17.
Eur J Med Chem ; 158: 393-404, 2018 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-30227353

RESUMO

One of the pathologic hallmarks in Alzheimer's disease (AD) is extracellular senile plaques composed of amyloid-ß (Aß) fibrils. Blocking Aß self-assembly or disassembling Aß aggregates by small molecules would be potential therapeutic strategies to treat AD. In this study, we synthesized a series of rationally designed divalent compounds and examined their effects on Aß fibrillization. A divalent amide (2) derived from two molecules of caffeic acid with a propylenediamine linker of ∼5.0 Šin length, which is close to the distance of adjacent ß sheets in Aß fibrils, showed good potency to inhibit Aß(1-42) fibrillization. Furthermore, compound 2 effectively dissociated the Aß(1-42) preformed fibrils. The cytotoxicity induced by Aß(1-42) aggregates in human neuroblastoma was reduced in the presence of 2, and feeding 2 to Aß transgenic C. elegans rescued the paralysis phenotype. In addition, the binding and stoichiometry of 2 to Aß(1-40) were demonstrated by using electrospray ionization-traveling wave ion mobility-mass spectrometry, while molecular dynamic simulation was conducted to gain structural insights into the Aß(1-40)-2 complex.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Ácidos Cafeicos/química , Ácidos Cafeicos/farmacologia , Fragmentos de Peptídeos/metabolismo , Doença de Alzheimer/tratamento farmacológico , Amidas/química , Amidas/farmacologia , Amidas/uso terapêutico , Peptídeos beta-Amiloides/ultraestrutura , Animais , Caenorhabditis elegans , Ácidos Cafeicos/uso terapêutico , Humanos , Modelos Moleculares , Fragmentos de Peptídeos/ultraestrutura , Multimerização Proteica/efeitos dos fármacos
18.
ACS Chem Neurosci ; 4(9): 1287-96, 2013 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-23805846

RESUMO

Amyloid-ß (Aß) and tau are the pathogenic hallmarks in Alzheimer's disease (AD). Aß oligomers are considered the actual toxic entities, and the toxicity relies on the presence of tau. Recently, Aß oligomers have been shown to specifically interact with cellular prion protein (PrP(C)) where the role of PrP(C) in AD is still not fully understood. To investigate the downstream mechanism of PrP(C) and Aß oligomer interaction and their possible relationships to tau, we examined tau expression in human neuroblastoma BE(2)-C cells transfected with murine PrP(C) and studied the effect under Aß oligomer treatment. By Western blotting, we found that PrP(C) overexpression down-regulated tau protein and Aß oligomer binding alleviated the tau reduction induced by wild type but not M128V PrP(C), the high AD risk polymorphic allele in human prion gene. PrP(C) lacking the Aß oligomer binding site was incapable of rescuing the level of tau reduction. Quantitative RT-PCR showed the PrP(C) effect was attributed to tau reduction at the transcription level. Treatment with Fyn pathway inhibitors, Fyn kinase inhibitor PP2 and MEK inhibitor U0126, reversed the PrP(C)-induced tau reduction and Aß oligomer treatment modulated Fyn kinase activity. The results suggested Fyn pathway regulated Aß-PrP(C)-tau signaling. Overall, our results demonstrated that PrP(C) down-regulated tau via the Fyn pathway and the effect can be regulated by Aß oligomers. Our study facilitated the understanding of molecular mechanisms among PrP(C), tau, and Aß oligomers.


Assuntos
Peptídeos beta-Amiloides/farmacologia , Fragmentos de Peptídeos/farmacologia , Proteínas PrPC/fisiologia , Proteínas Proto-Oncogênicas c-fyn/fisiologia , Proteínas tau/biossíntese , Doença de Alzheimer/genética , Animais , Butadienos/farmacologia , Linhagem Celular Tumoral , Regulação para Baixo , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Mutação de Sentido Incorreto , Nitrilas/farmacologia , Mutação Puntual , Proteínas PrPC/genética , Proteínas Proto-Oncogênicas c-fyn/antagonistas & inibidores , Pirimidinas/farmacologia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Proteínas Recombinantes de Fusão/metabolismo , Transdução de Sinais , Proteínas tau/genética
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