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Neuroinflammation is a critical feature in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD). Hesperetin can exert anti-inflammatory, antioxidant and other neuroprotective effects. In this study, the scopolamine (SCOP)-induced cognitive dysfunction in mice model was used to evaluate the neuroprotective effects of hesperetin. Behavioral tests (Morris water maze, open field, and novel object recognition tests) were conducted to evaluate the effect of hesperetin on cognitive dysfunction behaviors. Nissl staining and Immunofluorescence were used to evaluate hippocampal neuronal damage and microglial activation in mice. The levels of proinflammatory factors, oxidant stress, and the cholinergic neurotransmitter were detected by real-time quantitative fluorescence PCR (RT-qPCR) or biochemical reagent kits. Western blotting was used to detect the relative protein expression of the sirtuin 6 (SIRT6) / NOD-like receptor thermal protein domain associated protein 3 (NLRP3) pathway. Results showed that hesperetin could ameliorate SCOP-induced cognitive impairment and neuronal damage, and regulate the levels of cholinergic neurotransmitters in the hippocampal of AD mice. Hesperetin could also enhance antioxidant defense by regulating the levels of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT). Hesperetin exerted anti-neuroinflammation effects through inhibiting of microglia activation and down-regulating the mRNA transcript levels of inflammatory cytokines, such as tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS). Meanwhile, hesperetin could attenuate the expression of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), thioredoxin-interacting protein (TXNIP), and caspase-1 p20 and upregulate the expression of SIRT6 in SCOP-induced mice. Overall, our study suggested that hesperetin might ameliorate SCOP-induced cognitive dysfunction by improving cholinergic system dysfunction and suppressing oxidative stress and attenuating neuroinflammation via SIRT6/NLRP3 pathway in mice.
Assuntos
Disfunção Cognitiva , Fármacos Neuroprotetores , Sirtuínas , Camundongos , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamassomos/metabolismo , Antioxidantes , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Escopolamina , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/tratamento farmacológicoRESUMO
OBJECTIVES: To observe the effects of interactive scalp acupuncture on upper limb motor function and activities of daily living in patients with upper limb motor dysfunction after stroke. METHODS: One hundred and twenty patients with upper limb motor dysfunction after stroke were randomly divided into an observation group(60 cases, 2 cases dropped out)and a control group(60 cases, 1 case dropped out). Both groups were treated with routine medication and rehabilitation. The observation group was treated with interactive scalp acupuncture combined with suspension digital occupational therapy, interactive scalp acupuncture was applied at middle 2/5 of the parietal and temporal anterior oblique line, middle 2/5 of the parietal and temporal posterior oblique line and second lateral line of parietal of the hemiparalysis contralateral side, 30 min each time.The control group was treated with suspension digital occupational therapy alone. The treatment was given once a day, 5 times a week for 4 weeks in the two groups. The scores of Fugl-Meyer assessment scale of upper extremity(FMA-UE), action research arm test(ARAT), the modified Barthel index (MBI) and surface electromyography(sEMG)signal of the biceps and triceps on the affected side were observed before and after treatment in the two groups, and the clinical efficacy was evaluated. RESULTS: After treatment, the FMA-UE, ARAT and MBI scores were increased compared with those before treatment in both groups(P<0.05), the changes of the observation group were greater than those in the control group(P<0.05). After treatment, the integrated electromyography(iEMG)value and root mean square(RMS)value of the biceps and triceps on the affected side during elbow flexion and extension were increased compared with those before treatment in both groups(P<0.05), the changes of the observation group were greater than those in the control group(P<0.05). The total effective rate was 94.8%(55/58) in the observation group, which was higher than 83.1%(49/59) in the control group(P<0.05). CONCLUSIONS: Interactive scalp acupuncture could improve upper limb motor function and activities of daily living in patients with upper limb motor dysfunction after stroke.
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Terapia por Acupuntura , Terapia Ocupacional , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Atividades Cotidianas , Couro Cabeludo , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapia , Extremidade Superior , Resultado do TratamentoRESUMO
REBCO has been used extensively as coated conductors applied to superconducting magnets due to its exceptional superconducting properties. As a REBCO superconductor, YbBa2Cu3O7-y (Yb123) has a low melting temperature, making it suitable for use as an intermediate medium connector while preparing the superconducting joint. However, there is still uncertainty about the formation mechanism of Yb123 and the synthesis of this superconductor has not been fully understood. Therefore, this study systematically investigated the phase transformation process of Yb123 during heat treatment in flowing oxygen. The results indicated that Yb123 sample with the highest phase purity could be obtained by annealing at 927 °C or 937 °C but not in between, respectively. Furthermore, a quantitative phase analysis revealed that the sample annealed at 937 °C had a phase purity greater than 80 wt%. Additionally, a strong c-axis texture was observed in the bulk Yb123 superconductor prepared at 937 °C. Meanwhile, the superconducting results revealed that the bulk sample's Tc was 89.9 K, and its self-field critical current densities at 4.2 K and 77 K were 1.3 × 105 A/cm2 and 5.0 × 103 A/cm2, respectively. Based on the results mentioned above, the phase transformation process and formation mechanism of Yb123 in flowing oxygen were elaborated.
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BACKGROUND: Kai-Xin-San (KXS) has been reported to have a good curative impact on dementia. The purpose of the study was to determine whether KXS might ameliorate cognitive deficits in APP/PS1 mice and to evaluate its neuroprotective mechanism. METHODS: APP/PS1 mice were employed as an AD animal model; Aß1-42 and KXS-containing serum were used in HT22 cells. Four different behavioral tests were used to determine the cognitive ability of mice. Nissl staining was utilized to detect hippocampal neuron changes. ROS, SOD, and MDA were used to detect oxidative stress levels. Transmission electron microscopy and Western blot were used to evaluate mitochondrial morphology, mitochondrial division, and fusion state. Western blotting and immunofluorescence identified PSD95, BDNF, NGF, SYN, SIRT3, and NLRP3 inflammasome levels. RESULTS: The results indicated that KXS protected APP/PS1 mice against cognitive impairments. KXS suppressed neuronal apoptosis and oxidative stress among APP/PS1 mice. KXS and KXS-containing serum improved mitochondrial dysfunction and synaptic and neurotrophic factors regarding APP/PS1 mice. In addition, KXS and KXS-containing serum enhanced mitochondrial SIRT3 expression and reduced NLRP3 inflammasome expression in APP/PS1 mice. CONCLUSION: KXS improves cognitive dysfunction among APP/PS1 mice via regulating SIRT3-mediated neuronal cell apoptosis. These results suggested that KXS was proposed as a neuroprotective agent for AD progression.
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The bioavailability of most flavonoids is low but effective in vivo; however, the mechanism of the efficacy of flavonoids has not been elucidated. Kaempferol is typical flavonoids., preliminary research indicates that kaempferol has a significant anti-colon cancer and anti-inflammatory effect. We reported previously that the triple recycling pathways significantly increase the local bioavailability of flavonoids and prolong the residence time of flavonoids in the liver and intestines, which is likely the mode by which flavonoids exert local efficacy. Notably, Efflux transporters (ETs), such as Breast cancer resistance protein (BCRP) and Multi drug resistance-associated protein 2 (MRP2), are the main regulatory molecules of the enterohepatic triple recycling pathways. Thus, our current study explored the regulation of kaempferol by BCRP and MRP2 and the role of BCRP and MRP2 in the suppression of Dextran sulfate sodium (DSS)-induced colitis by kaempferol. Herein, four mouse model was constructed, and the Ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was established to simultaneously quantify kaempferol and its 3 metabolites and investigate the oral pharmacokinetic characteristics and tissue distribution of these compounds. In Bcrp-/--Mrp2-/- mice, the movement of kaempferol via the enterohepatic triple recycling was blocked, and the preventative and therapeutic effects of this compound on acute colitis were inhibited. BCRP and MRP2 defects hindered the efflux of kaempferol and its phase II metabolites and increased the plasma levels. Our study revealed that the disposal of kaempferol was regulated by the ETs BCRP and MRP2, and most importantly, the results will help elucidate the mechanism by which kaempferol suppresses the transformation of colitis into colon cancer.
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Colite , Neoplasias , Camundongos , Animais , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Quempferóis/farmacologia , Proteínas de Neoplasias/metabolismo , Proteínas Associadas à Resistência a Múltiplos Medicamentos , Espectrometria de Massas em Tandem , Transportadores de Cassetes de Ligação de ATP/metabolismo , Proteínas de Membrana Transportadoras , Colite/induzido quimicamente , Colite/tratamento farmacológicoRESUMO
Covalent organic frameworks (COFs) have attracted extensive interest due to their unique structures and various applications. However, structural diversities are still limited, which greatly restricts the development of COF materials. Herein, we report two unusual cubic (8-connected) building units and their derived 3D imine-linked COFs with bcu nets, JUC-588 and JUC-589. Owing to these unique building blocks with different sizes, the obtained COFs can be tuned to be microporous or mesoporous structures with high surface areas (2728 m2 g-1 for JUC-588 and 2482 m2 g-1 for JUC-589) and promising thermal and chemical stabilities. Furthermore, the high selectivity of CO2/N2 and CO2/CH4, excellent H2 uptakes, and efficient dye adsorption are observed. This research thus provides a general strategy for constructing stable 3D COF architectures with adjustable pores via improving the valency of rigid building blocks.
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High purity layered YbB2C2 powder is synthesized by a boro/carbothermic reduction method using YbBO3, B4C and graphite powders as raw materials. Its X-ray diffraction data are presented, and the space group P4/mbm (No. 127) is confirmed. The lattice parameters are a = b = 5.3389 Å and c = 3.5683 Å, and the atom positions are Yb (0.0000, 0.0000, 0.0000), B (0.3621, 0.8621, 0.5000), and C (0.1606, 0.6606, 0.5000). Porous YbB2C2 ceramics have a high porosity in the range of 69.89-58.11% and a high compressive strength in the range of 19.49-63.44 MPa. Furthermore, the as-produced porous YbB2C2 ceramics show unique chemical activity. Porous YbB2C2 ceramic with a porosity of 69.89% emits so much heat that it can burn a piece of paper when this ceramic is wetted by water. The rate of reaction between the porous YbB2C2 ceramic and water can be simply controlled by adjusting the porosity. The solid reaction products are YbB6, C and an unknown amorphous phase.
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BACKGROUND: Balance dysfunctions in stroke survivors are common and have significant impact on functional independence and rehabilitation. As a crucial technique of Traditional Chinese Medicine, acupuncture has been used widely for balance dysfunctions after stroke, although its effective evidence is not clear. Hence, we plan this systematic review protocol to evaluate the value of its efficacy and safety for balance dysfunctions after stroke. METHODS: We will search the databases from the publishment to April 2018: Web of Science, PubMed, Medline, Cochrane Library, EBASE, WHO International Clinical Trials Registry Platform, Wanfang, Chinese Biomedical Literature Database, Chinese Scientific Journal Database (VIP), and China National Knowledge Infrastructure. The clinical efficacy will be accepted as the primary outcomes. RevMan V.5.3 software will be used to compute the data synthesis when a meta-analysis is allowed. RESULTS: This systematic review and meta-analysis will provide a high-quality synthesis of current evidence of acupuncture for balance dysfunctions after stroke including clinical efficacy, balance ability, walking ability, and activity of daily life etcetera. CONCLUSION: This protocol will determine whether acupuncture is an effective and safety intervention for balance dysfunctions after stroke.