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1.
Neurosci Lett ; 715: 134611, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31698026

RESUMO

Continuous theta burst stimulation (cTBS) has been widely recognized as a therapeutic treatment for ischemic stroke, but the underlying mechanism is still elusive. Here, we investigated the protective effects of cTBS in the posterior parietal cortex during the chronic phase of stroke in the photothrombotic ischemic model. Infarction volume and neuron excitability in the peri-infarct area were assessed using immunohistochemistry and whole-cell patch-clamp. Spatial cognitive function was measured using the Morris water maze. Gamma-Amino butyric acid (GABA) interneurons were responsive to cTBS, and cTBS induced elevated phasic inhibition rather than tonic inhibition. Given that GABA-A-mediated phasic inhibition was elevated during the chronic phase of ischemic stroke for 30 days and was beneficial for stroke recovery, we investigated the therapeutic potential of cTBS in promoting functional recovery and found that the elevated phasic inhibition by cTBS improved spatial cognitive function in the photothrombotic stroke mouse model with induction in the posterior parietal cortex. Our study indicates the mechanism by which cTBS may modify the excitability of the brain cortex and provides novel insight into the potential of cTBS to protect against neuronal dysfunction in ischemic stroke.

2.
Brain Res ; 1726: 146488, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31586625

RESUMO

Acute ischemic stroke is a leading cause of disability with limited therapeutic options. Continuous theta burst stimulation (cTBS) has recently been shown to be a promising noninvasive therapeutic strategy for neuroprotection in ischemic stroke patients. Here, we investigated the protective effects of cTBS following acute infarction using a photothrombotic stroke (PTS) model in the right posterior parietal cortex (PPC) of C57BL/6 mice. Treatment with cTBS resulted in a reduction in the volume of the infarct region and significantly increased vascular diameter and blood flow velocity in peri-infarct region, as well as decreased the numbers of calcium binding adapter molecule 1 (Iba-1)-positive microglia and glial fibrillary acidic protein (GFAP)-positive astrocytes. Moreover, the number of CD16/32 positive microglia was decreased, whereas the number of CD206 positive microglia was increased. In addition, performance in a water maze task was significantly improved. These results indicated that cTBS protected against PPC infarct region, leading to an improvement in spatial cognitive function, possibly as a result of changes to cerebral microvascular function and inflammatory responses.

3.
Mater Sci Eng C Mater Biol Appl ; 105: 110042, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31546440

RESUMO

Influences of proteins on degradation of magnesium alloys are of great significance but not well understood. In particular the roles of amino acids, the basic unit of proteins in regulating the progress of biodegradation of magnesium based materials remain unclear. This study aims to investigate the impacts of alanine, glutamic acid and lysine on degradation of pure magnesium in phosphate buffer solution through SEM, XPS, FTIR, potentiodynamic polarisation curves, electrochemical impedance spectroscopy and immersion tests. The changed contents of amino acids in solutions were detected by UV-vis spectrophotometer. Results demonstrate that the charges of the selected amino acids imposed significant contribution to suppressing the degradation of pure magnesium in phosphate buffer solution. The presence of amino acids led to the formation of phosphate-based corrosion products, increasing free corrosion potential, and reduction in corrosion current density and solution pH depending on their isoelectric points and molecular structures. A plausible corrosion mechanism organised by amino acids on pure magnesium was proposed.


Assuntos
Aminoácidos/química , Magnésio/química , Fosfatos/química , Tampões (Química) , Corrosão , Espectroscopia Dielétrica , Eletroquímica , Humanos , Hidrogênio/análise , Ponto Isoelétrico , Conformação Molecular , Espectroscopia Fotoeletrônica , Espectroscopia de Infravermelho com Transformada de Fourier , Propriedades de Superfície , Difração de Raios X
4.
J Cereb Blood Flow Metab ; : 271678X19856226, 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31216943

RESUMO

Using a photothrombotic mouse model of single stroke, we show that a single stroke onset increases the nuclear factor-κB (NF-κB), NLR family CARD domain containing protein 4 (NLRC4), and absent in melanoma 2 (AIM2) inflammasomes, as well as the mRNA levels of NLRP3. Next, using a photothrombotic mouse model of recurrent stroke, we found that recurrent strokes increased the activation of NLRP3, exacerbated the brain damage and the pro-inflammatory response in wild type (WT) mice, but not in NLRP3 knockout (NLRP3 KO) mice. Additionally, we found that apoptosis-associated speck-like protein containing a CARD (ASC) protein level surrounding the infarct area was comparatively increased, but that ASC specks outside of microglia in both the ipsilateral and contralateral of stroke site were decreased in NLRP3 KO mice relative to wild-type (WT) controls, and the number of ASC specks surrounding the second infarct area was positively correlated to the damage scores. Mechanistically, we found that recombinant ASC (RecASC) activated NLRP3 and induced pro-inflammatory responses, exacerbating the outcome of ischemic stroke, in WT mice, but not in NLRP3 KO mice. We therefore conclude that the NLRP3 inflammasome is activated by two attacks of stroke, which act together with ASC to exacerbate recurrent strokes.

5.
Acta Biomater ; 98: 196-214, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31154057

RESUMO

A Zinc-loaded montmorillonite (Zn-MMT) coating was hydrothermally prepared using Zn2+ ion intercalated sodium montmorillonite (Na-MMT) upon magnesium (Mg) alloy AZ31 as bone repairing materials. Biodegradation rate of the Mg-based materials was studied via potentiodynamic polarization curves, electrochemical impedance spectroscopy (EIS) and hydrogen evolution tests. Results revealed that both Na-MMT and Zn-MMT coatings exhibited better corrosion resistance in Dulbecco's modified eagle medium (DMEM) + 10% calf serum (CS) than bare Mg alloy AZ31 counterparts. Hemolysis results demonstrated that hemocompatibility of the Na-MMT and Zn-MMT coatings were 5%, and lower than that of uncoated Mg alloy AZ31 pieces. In vitro MTT tests and live-dead stain of osteoblast cells (MC3T3-E1) indicated a significant improvement in cytocompatibility of both Na-MMT and Zn-MMT coatings. Antibacterial properties of two representative bacterial strains associated with device-related infection, i.e. Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), were employed to explore the antibacterial behavior of the coatings. The measured inhibitory zone and bacterial growth rate confirmed that Zn-MMT coatings exhibited higher suppression toward both E. coli and S. aureus than that of Na-MMT coatings. The investigation on antibacterial mechanism through scanning electron microscopy (SEM) and lactate dehydrogenase (LDH) release assay manifested that Zn-MMT coating led to severe breakage of bacterial membrane of E. coli and S. aureus, which resulted in a release of cytoplasmic materials from the bacterial cells. In addition, the good inhibition of Zn-MMT coatings against E. coli and S. aureus might be attributed to the slow but sustainable release of Zn2+ ions (up to 144 h) from the coatings into the culture media. This study provides a novel coating strategy for manufacturing biodegradable Mg alloys with good corrosion resistance, biocompatibility and antibacterial activity for future orthopedic applications. STATEMENT OF SIGNIFICANCE: The significance of the current work is to develop a corrosion-resistant and antibacterial Zn-MMT coating on magnesium alloy AZ31 through a hydrothermal method. The Zn-MMT coating on magnesium alloy AZ31 shows better corrosion resistance, biocompatibility and excellent antibacterial ability than magnesium alloy AZ31. This study provides a novel coating on Mg alloys for future orthopedic applications.

6.
Front Neurosci ; 13: 309, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31105511

RESUMO

Contralateral intermittent theta burst stimulation (iTBS) can potentially improve swallowing disorders with unilateral lesion of the swallowing cortex. However, the after-effects of iTBS on brain excitability remain largely unknown. Here, we investigated the alterations of temporal dynamics of inter-regional connectivity induced by iTBS following continuous TBS (cTBS) in the contralateral suprahyoid muscle cortex. A total of 20 right-handed healthy subjects underwent cTBS over the left suprahyoid muscle motor cortex and then immediately afterward, iTBS was applied to the contralateral homologous area. All of the subjects underwent resting-state functional magnetic resonance imaging (Rs-fMRI) pre- and post-TBS implemented on a different day. We compared the static and dynamic functional connectivity (FC) between the post-TBS and the baseline. The whole-cortical time series and a sliding-window correlation approach were used to quantify the dynamic characteristics of FC. Compared with the baseline, for static FC measurement, increased FC was found in the precuneus (BA 19), left fusiform gyrus (BA 37), and right pre/post-central gyrus (BA 4/3), and decreased FC was observed in the posterior cingulate gyrus (PCC) (BA 29) and left inferior parietal lobule (BA 39). However, in the dynamic FC analysis, post-TBS showed reduced FC in the left angular and PCC in the early windows, and in the following windows, increased FC in multiple cortical areas including bilateral pre- and postcentral gyri and paracentral lobule and non-sensorimotor areas including the prefrontal, temporal and occipital gyrus, and brain stem. Our results indicate that iTBS reverses the aftereffects induced by cTBS on the contralateral suprahyoid muscle cortex. Dynamic FC analysis displayed a different pattern of alteration compared with the static FC approach in brain excitability induced by TBS. Our results provide novel evidence for us in understanding the topographical and temporal aftereffects linked to brain excitability induced by different TBS protocols and might be valuable information for their application in the rehabilitation of deglutition.

7.
Front Behav Neurosci ; 13: 35, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30881294

RESUMO

Theta burst stimulation (TBS) is a powerful variant of repetitive transcranial magnetic stimulation (rTMS), making it potentially useful for the treatment of swallowing disorders. However, how dose TBS modulate human swallowing cortical excitability remains unclear. Here, we aim to measure the after-effects of spontaneous brain activity at resting-state using the regional homogeneity (ReHo) approach in healthy subjects who underwent different TBS protocols over the suprahyoid muscle cortex. Sixty healthy subjects (23.45 ± 2.73 years, 30 males) were randomized into three groups which completed different TBS protocols. The TMS coil was applied over the cortex of the suprahyoid muscles. Data of resting-state functional MRI (Rs-fMRI) of the subjects were acquired before and after TBS. The ReHo was compared across sessions [continuous TBS (cTBS), intermittent TBS (iTBS) and cTBS/iTBS] and runs (pre/post TBS). In the comparison between pre- and post-TBS, increased ReHo was observed in the right lingual gyrus and right precuneus and decreased ReHo in the left cingulate gyrus in the cTBS group. In the iTBS group, increased ReHo values were seen in the pre-/postcentral gyrus and cuneus, and decreased ReHo was observed in the left cerebellum, brainstem, bilateral temporal gyrus, insula and left inferior frontal gyrus. In the cTBS/iTBS group, increased ReHo was found in the precuneus and decreased ReHo in the right cerebellum posterior lobe, left anterior cerebellum lobe, and right inferior frontal gyrus. In the post-TBS inter-groups comparison, increased ReHo was seen in right middle occipital gyrus and decreased ReHo in right middle frontal gyrus and right postcentral gyrus (cTBS vs. cTBS/iTBS). Increased ReHo was shown in left inferior parietal lobule and left middle frontal gyrus (cTBS vs. iTBS). Increased ReHo was shown in right medial superior frontal gyrus and decreased ReHo in right cuneus (cTBS/iTBS vs. iTBS). Our findings indicate cTBS had no significant influence on ReHo in the primary sensorimotor cortex, iTBS facilitates an increased ReHo in the bilateral sensorimotor cortex and a decreased ReHo in multiple subcortical areas, and no reverse effect exhibits when iTBS followed the contralateral cTBS over the suprahyoid motor cortex. The results provide a novel insight into the neural mechanisms of TBS on swallowing cortex.

8.
Acta Biomater ; 79: 23-36, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30149212

RESUMO

Magnesium (Mg) and its alloys have become a research frontier in biodegradable materials owing to their superior biocompatibility and excellent biomechanical compatibility. However, their high degradation rate in the physiological environment should be well tackled prior to clinical applications. This review summarizes the latest progress in the development of polymeric coatings on biodegradable Mg alloys over the last decade, regarding preparation strategies for polylactic acid (PLA), poly (latic-co-glycolic) acid (PLGA), polycaprolactone (PCL), polydopamine (PDA), chitosan (CS), collagen (Col) and their composite, and their performance in terms of corrosion resistance and biocompatibility. Feasible perspectives and developing directions of next generation of polymeric coatings with respect to biomedical Mg alloys are briefly discussed. STATEMENT OF SIGNIFICANCE: Magnesium (Mg) and its alloys have become a research frontier in biodegradable materials owing to their superior biocompatibility and suitable biomechanical compatibility. However, the principal drawback of Mg-based implants is their poor corrosion resistance in physiological environments. Hence, it is vital to mitigate the degradation/corrosion behavior of Mg alloys for safe biomedical deployments. This review summarizes the latest progress in development of polymeric coatings on biomedical Mg alloys regarding preparation strategy, corrosion resistance and biocompatibility, including polylactic acid (PLA), poly (latic-co-glycolic) acid (PLGA), polycaprolactone (PCL), chitosan (CS), polydopamine (PDA), collagen (Col) and their composite. In addition, functionalized polymer coatings with Mg alloys exhibits a promising prospect owing to their ability of degradation along with biocompatibility, self-healing, drug-delivery and osteoinduction.


Assuntos
Ligas/farmacologia , Materiais Revestidos Biocompatíveis/farmacologia , Magnésio/farmacologia , Polímeros/farmacologia , Corrosão , Humanos
9.
Int J Mol Med ; 42(4): 1935-1944, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30085336

RESUMO

Aging is associated with impairment of the paravascular pathway caused by the activation of astrocytes and depolarization of protein aquaporin­4 (AQP4) water channels, resulting in the accumulation of protein waste, including amyloid ß (Aß), in the brain parenchyma. The secreted glycoprotein slit guidance ligand 2 (Slit2) is important in regulating the function of the central nervous system and inflammatory response process. In the present study, 15­month­old Slit2 overexpression transgenic mice (Slit2­Tg mice) and two­photon fluorescence microscopy were used to evaluate the dynamic clearance of the paravascular pathway and the integrity of the blood­brain barrier (BBB). The reactivity of astrocytes, polarity of AQP4 and deposition of Aß in the brain parenchyma were analyzed by immunofluorescence. A Morris water maze test was used to examine the effect of Slit2 on spatial memory cognition in aging mice. It was found that the overexpression of Slit2 improved the clearance of the paravascular pathway by inhibiting astrocyte activation and maintaining AQP4 polarity on the astrocytic endfeet in Slit2­Tg mice. In addition, Slit2 restored the disruption of the BBB caused by aging. The accumulation of Aß was significantly reduced in the brain of Slit2­Tg mice. Furthermore, the water maze experiment showed that Slit2 improved spatial memory cognition in the aging mice. These results indicated that Slit2 may have the potential to be used in the prevention and treatment of neurodegenerative diseases in the elderly.


Assuntos
Encéfalo/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Envelhecimento/fisiologia , Animais , Aquaporina 4 , Astrócitos/citologia , Astrócitos/metabolismo , Barreira Hematoencefálica/metabolismo , Feminino , Imunofluorescência , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Masculino , Aprendizagem em Labirinto/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas do Tecido Nervoso/genética , Memória Espacial/fisiologia
10.
Front Cell Neurosci ; 12: 177, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29997480

RESUMO

While increasing evidence demonstrated that voluntary wheel running promotes cognitive function, little is known on how different types of voluntary wheel running affect cognitive function in elderly populations. We investigated the effects of various voluntary wheel-running types on adult hippocampal neurogenesis and spatial cognition in middle-aged mice. Male C57BL6 and Thy1-green fluorescent protein (GFP) transgenic mice (13 months) were equally assigned to one of the following groups: (1) T1: no voluntary wheel running; (2) T2: intermittent voluntary wheel running; and (3) T3: continuous voluntary wheel running. The Thy1-GFP transgenic mice were used to specifically label granule cells, since Thy-1 is a promoter for neuronal expression. Behavioral evaluations suggested that intermittent voluntary wheel running improved Morris water maze performance in middle-aged mice. The number of BrdU-positive cells was significantly higher in both intermittent and continuous voluntary wheel running compared with no voluntary wheel running. However, only intermittent voluntary wheel running facilitated the newborn cells to differentiate into granule cells, while newborn cells tended to differentiate into astrocytes and repopulation of microglia was also enhanced in the continuous voluntary wheel-running group. These results indicated that intermittent voluntary exercise may be more beneficial for enhancing spatial memory. Effective improvement of hippocampal neurogenesis was also caused by intermittent voluntary wheel running in middle-aged mice.

11.
Bioact Mater ; 3(3): 245-249, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29744463

RESUMO

A SnO2-doped dicalcium phosphate coating was prepared on AZ31 alloy by means of hydrothermal deposition. The results showed that the coating possessed a globular morphology with a long lamellar crystalline structure and a thickness of approximately 40 µm. The surface of the coating became smooth with an increase additive amount of the SnO2 nanoparticles. The corrosion current density and hydrogen evolution rate of the coating prepared in presence of SnO2 were reduced compared to the coating without SnO2 and the bare AZ31 substrate, indicating an improvement in the corrosion resistance of the SnO2-doped coating.

12.
Eur J Med Chem ; 145: 498-510, 2018 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-29335211

RESUMO

Novel topoisomerase II (Topo II) inhibitors have gained considerable interest for the development of anticancer agents. In this study, a series of carbazole derivatives containing chalcone analogs (CDCAs) were synthesized and investigated for their Topo II inhibition and cytotoxic activities. The results from Topo II mediated DNA relaxation assay showed that CDCAs could significantly inhibit the activity of Topo II, and the structure-activity relationship indicated the halogen substituent in phenyl ring play an important role in the activity. Further mechanism studies revealed that CDCAs function as non-intercalative Topo II catalytic inhibitors. Moreover, some CDCAs showed micromolar cytotoxic activities. The most potent compound 3h exhibited notable growth inhibition against four human cancer cell lines. Flow cytometric analysis revealed that compounds 3d and 3h arrested the HL-60 cells in sub G1 phase by induction of apoptosis. It was further confirmed by Annexin-V-FITC binding assay. Western blot analysis revealed that compound 3h induces apoptosis likely through the activation of caspase proteins.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Carbazóis/farmacologia , Chalcona/farmacologia , DNA Topoisomerases Tipo II/metabolismo , Inibidores da Topoisomerase II/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Biocatálise , Carbazóis/síntese química , Carbazóis/química , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Chalcona/química , Clivagem do DNA/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células HL-60 , Humanos , Estrutura Molecular , Plasmídeos , Relação Estrutura-Atividade , Inibidores da Topoisomerase II/síntese química , Inibidores da Topoisomerase II/química
13.
Plant Cell ; 30(2): 397-414, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29367305

RESUMO

Establishment of symbiosis between legumes and nitrogen-fixing rhizobia depends on bacterial Nod factors (NFs) that trigger symbiosis-related NF signaling in host plants. NFs are modified oligosaccharides of chitin with a fatty acid moiety. NFs can be cleaved and inactivated by host enzymes, such as MtNFH1 (MEDICAGO TRUNCATULA NOD FACTOR HYDROLASE1). In contrast to related chitinases, MtNFH1 hydrolyzes neither chitin nor chitin fragments, indicating a high cleavage preference for NFs. Here, we provide evidence for a role of MtNFH1 in the symbiosis with Sinorhizobium meliloti Upon rhizobial inoculation, MtNFH1 accumulated at the curled tip of root hairs, in the so-called infection chamber. Mutant analysis revealed that lack of MtNFH1 delayed rhizobial root hair infection, suggesting that excess amounts of NFs negatively affect the initiation of infection threads. MtNFH1 deficiency resulted in nodule hypertrophy and abnormal nodule branching of young nodules. Nodule branching was also stimulated in plants expressing MtNFH1 driven by a tandem CaMV 35S promoter and plants inoculated by a NF-overproducing S. meliloti strain. We suggest that fine-tuning of NF levels by MtNFH1 is necessary for optimal root hair infection as well as for NF-regulated growth of mature nodules.


Assuntos
Regulação da Expressão Gênica de Plantas , Hidrolases/metabolismo , Medicago truncatula/enzimologia , Transdução de Sinais , Sinorhizobium meliloti/fisiologia , Simbiose , Quitina/metabolismo , Hidrolases/genética , Medicago truncatula/genética , Medicago truncatula/microbiologia , Oligossacarídeos/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Nódulos Radiculares de Plantas/enzimologia , Nódulos Radiculares de Plantas/genética , Nódulos Radiculares de Plantas/microbiologia
14.
Inflammation ; 41(2): 515-529, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29198013

RESUMO

Brain dysfunction is a common complication after sepsis and is an independent risk factor for a poor prognosis, which is partly attributed to the dysregulated inflammatory response and oxidative damage. Melatonin regulates the sleep-wake cycle and also has potent anti-inflammatory and antioxidant properties, yet the protective effects of melatonin on sepsis-induced neurobehavioral dysfunction remain to be elucidated. In the present study, melatonin was administered intraperitoneally daily at a dose of 10 mg/kg for three consecutive days immediately (early treatment) or 7 days (delayed treatment) after sham operation or cecal ligation and puncture (CLP), followed by an additional treatment in drinking water until the end of behavioral tests. The concentrations of pro-inflammatory cytokines (tumor necrosis factor (TNF-α), interleukin-1ß (IL-1ß), IL-6, IL-10), malondialdehyde (MDA), superoxide dismutase (SOD), reactive oxygen species (ROS), brain-derived neurotrophic factor (BDNF), and glial cell line-derived neurotrophic factor (GDNF) were determined at the indicated time points. Compared with the CLP + vehicle group, we found that early melatonin treatment resulted in increased survival rate but not improvement in measures of neurobehavioral outcomes, which was accompanied by significantly lower plasma level of IL-1ß. Intriguingly, delayed melatonin treatment improved neurobehavioral dysfunction by normalization of hippocampal BDNF and GDNF expressions. In conclusion, our study suggests the beneficial effects of both early and delayed melatonin treatment after sepsis development, which implicates melatonin has a potential therapeutic value in sepsis-associated organ damage including brain dysfunction.


Assuntos
Melatonina/farmacologia , Encefalopatia Associada a Sepse/tratamento farmacológico , Animais , Comportamento Animal/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Citocinas/análise , Fator Neurotrófico Derivado de Linhagem de Célula Glial , Hipocampo/metabolismo , Melatonina/administração & dosagem , Melatonina/uso terapêutico , Camundongos , Substâncias Protetoras/farmacologia , Taxa de Sobrevida , Fatores de Tempo
15.
Mol Nutr Food Res ; 62(2)2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28849618

RESUMO

SCOPE: Curcuma longa (turmeric) is a folk medicine in South and Southeast Asia, which has been widely used to alleviate chronic inflammation. Aromatic-turmerone is one of the main components abundant in turmeric essential oil. However, little information is available from controlled studies regarding its biological activities and underlying molecular mechanisms against chronic inflammation in the brain. In the current study, we employed a classical LPS model to study the effect and mechanism of aromatic-turmerone on neuroinflammation. METHODS AND RESULTS: The effects of aromatic-turmerone were studied in LPS-treated mice and BV2 cells. The cognitive function assays, protein analyses, and histological examination were performed. Oral administration of aromatic-turmerone could reverse LPS-induced memory disturbance and normalize glucose intake and metabolism in the brains of mice. Moreover, aromatic-turmerone significantly limited brain damage, through inhibiting the activation of microglia and generation of inflammatory cytokines. Further study in vitro revealed that aromatic-turmerone targeted Toll-like receptor 4 mediated downstream signaling, and lowered the release of inflammatory mediators. CONCLUSION: These observations indicate that aromatic-turmerone is effective in preventing brain damage caused by neuroinflammation and may be useful in the treatment of neuronal inflammatory diseases.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Inflamação/tratamento farmacológico , Cetonas/farmacologia , Transtornos da Memória/tratamento farmacológico , Sesquiterpenos/farmacologia , Receptor 4 Toll-Like/metabolismo , Administração Oral , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Inflamação/induzido quimicamente , Inflamação/metabolismo , Cetonas/administração & dosagem , Lipopolissacarídeos/toxicidade , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/induzido quimicamente , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Microglia/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Sesquiterpenos/administração & dosagem , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/genética
16.
Neuroscience ; 365: 48-56, 2017 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-28947393

RESUMO

Theta burst stimulation (TBS) has emerged as a promising tool for the treatment of swallowing disorders; however, the short-term after-effects of brain activation induced by TBS remain unknown. Here, we measured the changes in spontaneous brain activation using the amplitude of low-frequency fluctuation (ALFF) approach in subjects who underwent different TBS protocols. Sixty right-handed healthy participants (male, n=30; female, n=30; mean age=23.5y) were recruited in this study and randomly assigned to three groups that underwent three different TBS protocols. In group 1, continuous TBS (cTBS) was positioned on the left hemisphere of the suprahyoid muscle cortex. For group 2, intermittent TBS (iTBS) was placed on the left hemisphere of the suprahyoid muscle cortex. Group 3 underwent combined cTBS/iTBS protocols in which iTBS on the right hemisphere was performed immediately after completing cTBS on the left suprahyoid muscle cortex. Compared to pre-TBS, post-cTBS showed decreased ALFF in the anterior cingulate gyrus (BA 32); post-iTBS induced an increase in ALFF in the bilateral precuneus (BA 7); and post-cTBS/iTBS induced a decrease in ALFF in the brainstem, and resulted in increased ALFF in the middle cingulate gyrus (BA 24) as well as the left precentral gyrus (BA 6). Compared the effect of post-TBS protocols, increased ALFF was found in left posterior cerebellum lobe and left inferior parietal lobule (BA 40) (post-cTBS vs post-iTBS), and decreased ALFF exhibited in paracentral lobule (BA 4) (post-iTBS vs post-cTBS/iTBS). These findings indicate that multiple brain areas involved in swallowing regulation after stimulation of TBS over the suprahyoid muscles. cTBS induces decreased after-effects while iTBS results in increased after-effects on spontaneous brain activation. Moreover, iTBS can eliminate the after-effects of cTBS applied on the contralateral swallowing cortex and alter the activity of contralateral motor cortex and brainstem. Our findings provide a novel evidence for the short-term effect of TBS on spontaneous brain activation.


Assuntos
Córtex Motor/diagnóstico por imagem , Músculos do Pescoço/fisiologia , Estimulação Magnética Transcraniana/métodos , Adulto , Vias Aferentes/fisiologia , Análise de Variância , Biofísica , Feminino , Voluntários Saudáveis , Humanos , Processamento de Imagem Assistida por Computador , Imagem por Ressonância Magnética , Masculino , Músculos do Pescoço/diagnóstico por imagem , Distribuição Aleatória , Adulto Jovem
17.
Materials (Basel) ; 10(7)2017 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-28773085

RESUMO

The influences of glucose and amino acid (L-cysteine) on the degradation of pure magnesium have been investigated using SEM, XRD, Fourier transformed infrared (FTIR), X-ray photoelectron spectroscopy (XPS), polarization and electrochemical impedance spectroscopy and immersion tests. The results demonstrate that both amino acid and glucose inhibit the corrosion of pure magnesium in saline solution, whereas the presence of both amino acid and glucose accelerates the corrosion rate of pure magnesium. This may be due to the formation of -C=N- bonding (a functional group of Schiff bases) between amino acid and glucose, which restricts the formation of the protective Mg(OH)2 precipitates.

18.
Biol Pharm Bull ; 40(8): 1247-1254, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28769006

RESUMO

Metformin is a commonly used drug for the treatment of type II diabetes and atorvastatin is the most prescribed cholesterol-lowering statin. The present study investigated the effects and mechanisms of metformin and atorvastatin in combination on human prostate cancer cells cultured in vitro and grown as xenograft tumor in vivo. Metformin in combination with atorvastatin had stronger effects on growth inhibition and apoptosis in PC-3 cells than either drug alone. The combination also potently inhibited cell migration and the formation of tumorspheres. Metformin and atorvastatin in combination had a potent inhibitory effect on nuclear factor-kappaB (NF-κB) activity and caused strong decreases in the expression of its downstream anti-apoptotic gene Survivin. Moreover, strong decreases in the levels of phospho-Akt and phosphor-extracellular signal-regulated kinase (Erk)1/2 were found in the cells treated with the combination. The in vivo study showed that treatment of severe combined immunodeficient (SCID) mice with metformin or atorvastatin alone resulted in moderate inhibition of tumor growth while the combination strongly inhibited the growth of the tumors. Results of the present study indicate the combination of metformin and atorvastatin may be an effective strategy for inhibiting the growth of prostate cancer and should be evaluated clinically.


Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Atorvastatina/uso terapêutico , Metformina/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Atorvastatina/farmacologia , Linhagem Celular Tumoral , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Proteínas Inibidoras de Apoptose/metabolismo , Masculino , Metformina/farmacologia , Camundongos SCID , NF-kappa B/metabolismo , Neoplasias da Próstata/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Survivina , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Neurosci Lett ; 653: 189-194, 2017 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-28576566

RESUMO

Sleep deprivation (SD) is a common condition associated with a variety of nervous system diseases, and has a negative impact on emotional and cognitive function. Continuous theta burst stimulation (cTBS) is known to improve cognition and emotion function in normal situations as well as in various types of dysfunction, but the mechanism remains unknown. We used two-photon in vivo imaging to explore the effect of cTBS on glymphatic pathway clearance in normal and SD C57BL/6J mice. Aquaporin-4 (AQP4) polarization was detected by immunofluorescence. Anxiety-like behaviors was measured using open field tests. We found that SD reduced influx efficiency along the peri-vascular space (PVS), disturbed AQP4 polarization and induced anxiety-like behaviors. CTBS significantly attenuated the decrease in efficiency of solute clearance usually incurred with SD, restored the loss of AQP4 polarization and improved anxiety-like behavior in SD animals. Our results implied that cTBS had the potential to protect against neuronal dysfunction induced by sleep disorders.


Assuntos
Encéfalo/metabolismo , Taxa de Depuração Metabólica , Privação do Sono/metabolismo , Animais , Ansiedade , Aquaporina 4/metabolismo , Encéfalo/fisiopatologia , Estimulação Elétrica , Masculino , Camundongos Endogâmicos C57BL , Privação do Sono/líquido cefalorraquidiano
20.
Front Mol Neurosci ; 10: 144, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28579942

RESUMO

Age is characterized by chronic inflammation, leading to synaptic dysfunction and dementia because the clearance of protein waste is reduced. The clearance of proteins depends partly on the permeation of the blood-brain barrier (BBB) or on the exchange of water and soluble contents between the cerebrospinal fluid (CSF) and the interstitial fluid (ISF). A wealth of evidence indicates that physical exercise improves memory and cognition in neurodegenerative diseases during aging, such as Alzheimer's disease (AD), but the influence of physical training on glymphatic clearance, BBB permeability and neuroinflammation remains unclear. In this study, glymphatic clearance and BBB permeability were evaluated in aged mice using in vivo two-photon imaging. The mice performed voluntary wheel running exercise and their water-maze cognition was assessed; the expression of the astrocytic water channel aquaporin 4 (AQP4), astrocyte and microglial activation, and the accumulation of amyloid beta (Aß) were evaluated with immunofluorescence or an enzyme-linked immunosorbent assay (ELISA); synaptic function was investigated with Thy1-green fluorescent protein (GFP) transgenic mice and immunofluorescent staining. Voluntary wheel running significantly improved water-maze cognition in the aged mice, accelerated the efficiency of glymphatic clearance, but which did not affect BBB permeability. The numbers of activated astrocytes and microglia decreased, AQP4 expression increased, and the distribution of astrocytic AQP4 was rearranged. Aß accumulation decreased, whereas dendrites, dendritic spines and postsynaptic density protein (PSD95) increased. Our study suggests that voluntary wheel running accelerated glymphatic clearance but not BBB permeation, improved astrocytic AQP4 expression and polarization, attenuated the accumulation of amyloid plaques and neuroinflammation, and ultimately protected mice against synaptic dysfunction and a decline in spatial cognition. These data suggest possible mechanisms for exercise-induced neuroprotection in the aging brain.

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