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The physical and chemical properties of spinnable pitch showed a huge impact on the performance of resultant pitch carbon fiber even if its physical and chemical properties were slightly changed. Various polycyclic aromatic compounds and abundant free radicals existed in spinnable pitch, and there are many interactions among molecules and free radicals. The molecular structure and composition of spinnable pitch were investigated during incubation, and the effect of molecular evaluation on rheological properties of spinnable pitch was illustrated using various characterization methods in this work. It indicated that n-hexane soluble fraction mainly occurred condensation or cleavage, and a small number of heavy components were generated after a long period. The fraction of n-hexane insoluble/toluene soluble underwent molecular condensation and cross-linking in the presence of oxygen-containing radicals and aromatic hydrocarbon radicals, while toluene insoluble/tetrahydrofuran soluble fraction tended to change in large molecules of polycyclic aromatic hydrocarbons. Lastly, tetrahydrofuran insoluble fraction was condensed due to its high aromaticity during the incubation process, and the content of aromatic carbon increased. These changes of composition and structure of spinnable pitch led to its softening point, increase in viscosity and flow activation energy, and deterioration of the rheological property.
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Reactive oxygen species formed within the mammalian cell can produce 8-oxo-7,8-dihydroguanine (8-oxoG) in mRNA, which can cause base mispairing during gene expression. Here we found that administration of 8-oxoGTP in MTH1-knockdown cells results in increased 8-oxoG content in mRNA. Under this condition, an amber mutation of the reporter luciferase is suppressed. Using second-generation sequencing techniques, we found that U-to-G changes at preassigned sites of the luciferase transcript increased when 8-oxoGTP was supplied. In addition, an increased level of 8-oxoG content in RNA induced the accumulation of aggregable amyloid ß peptides in cells expressing amyloid precursor protein. Our findings indicate that 8-oxoG accumulation in mRNA can alter protein synthesis in mammalian cells. Further work is required to assess the significance of these findings under normal physiological conditions.
Assuntos
Guanina/análogos & derivados , Mutagênese/genética , Biossíntese de Proteínas/genética , Transcrição Gênica/genética , Peptídeos beta-Amiloides/genética , Anticódon/genética , Pareamento de Bases , Códon sem Sentido , Enzimas Reparadoras do DNA/antagonistas & inibidores , Enzimas Reparadoras do DNA/genética , Técnicas de Silenciamento de Genes , Genes Reporter , Guanina/química , Células HeLa , Humanos , Luciferases/genética , Monoéster Fosfórico Hidrolases/antagonistas & inibidores , Monoéster Fosfórico Hidrolases/genética , Interferência de RNA , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Espécies Reativas de OxigênioRESUMO
Cancer stem-like cells (CSLCs) are involved in cancer initiation, development, and metastasis, and microRNAs (miRNAs) play pivotal roles in regulating CSLCs. miRNA-based therapeutic strategy associated with CSLCs might promise potential new therapeutic approaches. In the present study, we found that miR-1290 was increased in CD133(+) cells. Antagomir-1290 significantly suppressed tumor volume and weight initiated by CD133(+) cells in vivo. Furthermore, antagomir-1290 significantly inhibited the proliferation, clonogenicity, invasion, and migration of CD133(+) cells by targeting fyn-related Src family tyrosine kinase. These findings provide insights into the clinical prospect of miR-1290-based therapies for non-small cell lung cancer.
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Antígenos CD/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Glicoproteínas/genética , MicroRNAs/biossíntese , Proteínas de Neoplasias/biossíntese , Peptídeos/genética , Proteínas Tirosina Quinases/biossíntese , Antígeno AC133 , Carcinogênese/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/antagonistas & inibidores , Invasividade Neoplásica/genética , Proteínas de Neoplasias/genética , Células-Tronco Neoplásicas/patologia , Proteínas Tirosina Quinases/genéticaRESUMO
Lung cancer is the major cause of cancer related lethality worldwide, and metastasis to distant organs is the pivotal cause of death for the vast majority of lung cancer patients. Accumulated evidence indicates that lung cancer stem-like cells (CSLCs) play important roles in metastagenesis, and these circulating CSLCs may be important targets to inhibit the subsequent metastasis. The present study was aimed at establishing CSLC-targeting polylactic acid (PLA) encapsulated docetaxel nanoparticles for antimetastatic therapy. Cyclic binding peptides were screened on CSLCs in vitro and the peptide CVKTPAQSC exhibiting high specific binding ability to pulmonary adenocarcinoma tissue was subsequently conjugated to the nanoparticles loaded with docetaxel (NDTX). Antimetastatic effect of CSLC-targeting nanoparticles loaded with docetaxel (TNDTX) was evaluated in a nude mouse model of liver metastasis. Results showed that, in the absence of targeting peptide, NDTX hardly exhibited any antimetastatic effect. However, TNDTX treatment significantly decreased the metastatic tumor area in the nude mouse liver. Histopathological and serological results also confirmed the antimetastatic efficacy of TNDTX. To our knowledge, this is the first report on establishing a CSLC-based strategy for lung cancer metastatic treatment, and we hope this will offer a potential therapeutic approach for management of metastatic lung cancer.
Assuntos
Antineoplásicos/administração & dosagem , Ácido Láctico/química , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Células Neoplásicas Circulantes/efeitos dos fármacos , Polímeros/química , Taxoides/administração & dosagem , Antígeno AC133 , Animais , Antígenos CD/metabolismo , Peso Corporal , Linhagem Celular Tumoral , Docetaxel , Portadores de Fármacos , Feminino , Glicoproteínas/metabolismo , Fígado/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Nanomedicina , Nanopartículas/química , Metástase Neoplásica , Peptídeos/química , Peptídeos/metabolismo , PoliésteresRESUMO
The basic ionic liquid 1-ethyl-3-methylimidazolium acetate ([C2C1Im][OAc]) could efficiently catalyze the conversion of 2-amino-2-deoxy-d-glucose (GlcNH2) into deoxyfructosazine (DOF) and fructosazine (FZ). Mechanistic investigation by NMR studies disclosed that [C2C1Im][OAc], exhibiting strong hydrogen bonding basicity, could coordinate with the hydroxyl and amino groups of GlcNH2via the promotion of hydrogen bonding in bifunctional activation of substrates and further catalyzing product formation, based on which a plausible reaction pathway involved in this homogeneous base-catalyzed reaction was proposed. Hydrogen bonding as an activation force, therefore, is responsible for the remarkable selectivity and rate enhancement observed.
Assuntos
Glucosamina/síntese química , Imidazóis/química , Catálise , Glucosamina/química , Espectroscopia de Ressonância Magnética , Estrutura MolecularRESUMO
OBJECTIVE: To explore the changes over time of cannabinoid receptor 1 (CB1R) in hippocampus of status epilepticus (SE) rats. METHODS: A rat model of SE was established by an intraperitoneal injection of kainic acid (KA). The animals were scarified 30 minutes later. And the changes of CB1lR were detected by immunohistochemistry and Western blot at 4 hours, 1 day, 1 week, 1 month and 2 months post-SE. RESULTS: CB1R in CAl area of hippocampus of SE rats increased gradually at 1 week and then decreased to normal afterward (KA vs NS: 5. 5 ± 1. 1 vs 1.8 ± 0. 2, 6. 4 ± 3. 7 vs 3. 1 ± 0. 7, 16. 9 ± 10. 4 vs 3. 7 ± 1. 7, 8. 8 ± 5. 4 vs 6. 9 ± 4. 0, 3. 2 ± 1. 0 vs 4.4 ± 1. 9). And CBlR in area of CA3, DG had the same trend as CAI. The IA of CBl R significantly increased at 1 week (P <0. 05) and insignificantly deceased after 1 week (P > 0. 05). CONCLUSION: There is a protective increase of CB1R in hippocampus of SE rats and then it returns to normal. Thus CB1R may he involved in the occurrences and terminations of seizures.
Assuntos
Hipocampo , Estado Epiléptico , Animais , Canabinoides , Ácido Caínico , Ratos , Receptor CB1 de Canabinoide , ConvulsõesRESUMO
Changes in the structure and number of synapses modulate learning, memory and cognitive disorders. Ubiquitin-mediated protein modification is a key mechanism for regulating synaptic activity, though the precise control of this process remains poorly understood. RING finger protein 13 (RNF13) is a recently identified E3 ubiquitin ligase, and its in vivo function remains completely unknown. We show here that genetic deletion of RNF13 in mice leads to a significant deficit in spatial learning as determined by the Morris water maze test and Y-maze learning test. At the ultrastructral level, the synaptic vesicle density was decreased and the area of the active zone was increased at hippocampal synapses of RNF13-null mice compared with those of wild-type littermates. We found no change in the levels of SNARE (soluble N-ethylmaleimide-sensitive factor-attachment protein receptor) complex proteins in the hippocampus of RNF13-null mice, but impaired SNARE complex assembly. RNF13 directly interacted with snapin, a SNAP-25-interacting protein. Interestingly, snapin was ubiquitinated by RNF13 via the lysine-29 conjugated polyubiquitin chain, which in turn promoted the association of snapin with SNAP-25. Consistently, we found an attenuated interaction between snapin and SNAP-25 in the RNF13-null mice. Therefore, these results suggest that RNF13 is involved in the regulation of the SNARE complex, which thereby controls synaptic function.
Assuntos
Proteínas SNARE/metabolismo , Ubiquitina-Proteína Ligases/fisiologia , Animais , Hipocampo/metabolismo , Hipocampo/ultraestrutura , Aprendizagem em Labirinto/fisiologia , Camundongos , Camundongos Knockout , Sinapses/genética , Sinapses/ultraestrutura , Vesículas Sinápticas/genética , Vesículas Sinápticas/ultraestrutura , Proteína 25 Associada a Sinaptossoma/metabolismo , Proteína 25 Associada a Sinaptossoma/fisiologia , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação , Proteínas de Transporte Vesicular/metabolismoRESUMO
Pitch-based porous carbons with adjustable surface chemical property and controllable pore structure are regarded as promising cathode materials for aqueous zinc-ion hybrid capacitors (ZIHCs), while its disordered carbon matrix and microstructure as well as insufficient surface defects often result in low Zn2+-storage capacity and poor rate capability of ZIHCs. Herein, a synergetic strategy of self-assembled supermolecule and enriched defective carbon engineering was developed to achieve ultrahigh edge-nitrogen doping for ZIHCs. The crystallite defects and surface structure of porous carbon could be effectively achieved through grafting electronegative oxygen-containing small molecules and high-level nitrogen-containing functional groups between modified polycyclic aromatic hydrocarbon and supermolecule framework. The optimized three-dimensional carbon structure delivered high capacity of 218â mAh g-1 at 0.2â A g-1, fast charge/discharge capability, enhanced energy density (165.4â Wh kg-1) and superior cycling stability (95 % retention after 10000 cycles as cathode of ZIHCs). This provided new insight into the controllable synthesis of carbon cathodes for ZIHCs and expects to prepare functional porous carbon by supermolecules and special precursors.
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The development of high-performance bifunctional electrocatalysts for oxygen evolution reaction and heavy metal ion (HMI) detection is significant and challenging. Here, a novel nitrogen, sulfur co-doped porous carbon sphere bifunctional catalyst was designed and fabricated by hydrothermal followed by carbonization using starch as carbon source and thiourea as nitrogen, sulfur source for HMI detection and oxygen evolution reactions. Under the synergistic effect of pore structure, active sites and nitrogen, sulfur functional groups, C-S0.75-HT-C800 demonstrated excellent HMI detection performance and oxygen evolution reaction activity. Under optimized conditions, the detection limits (LODs) of C-S0.75-HT-C800 sensor were 3.90, 3.86 and 4.91 nM for Cd2+, Pb2+ and Hg2+ when detected individually; and the sensitivities were 13.12, 19.50 and 21.19 µA/µM. The sensor also obtained high recoveries of Cd2+, Hg2+ and Pb2+ in river water samples. During the oxygen evolution reaction, a Tafel slope of 70.1 mV/dec and a low overpotential of 277 mV were obtained for C-S0.75-HT-C800 electrocatalyst with a current density of 10 mA/cm2 in basic electrolyte. This research offers a neoteric and simple strategy in the design as well as fabrication of bifunctional carbon-based electrocatalysts.
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Some anesthetics have been suggested to induce Alzheimer's disease (AD) neuro-pathogenesis. Increasing evidence indicates that hyperphosphorylated tau plays a key role in the pathogenic events that occur in AD. Isoflurane has been shown to induce apoptosis, which leads to accumulation of amyloid-ß (Aß). We set out to investigate whether isoflurane can induce apoptosis by increasing hyperphosphorylated tau in Aß25-35-induced cells and the underlying mechanism. Cultured rat pheochromocytoma cells (PC12) were exposed to 20 mM Aß25-35 alone or with 2% isoflurane for 6 h. The cell viability was determined by MTT assay, and the apoptosis rate was detected by flowcytometry. Western blotting and immunocytochemical staining were performed to observe the protein expression of Bcl-2 family, tau phosphorylation of different sites, tau protein kinases and phosphatases. Additionally, lithium chloride was administered to all above groups to investigate the changes of apoptosis rate and protein expression. The apoptosis rate was significantly increased in Aß25-35 group compared with the others groups, which was accompanied by bcl-2 decline, and the phosphorylation of glycogen synthase kinase-3ß (GSK-3ß) and tau of two sites increased. LiCl attenuated the cellular apoptosis by inhibition the level of tau phosphorylation. Isoflurane upregulated the level of phosphorylated GSK-3ß, which phosphorylate tau at different sites, and aggravated the apoptotic rate of the Aß25-35-induced PC12 cells. It indicated that isoflurane-induced tau phosphorylation might play a role in the AD-like development.
Assuntos
Peptídeos beta-Amiloides/toxicidade , Apoptose/efeitos dos fármacos , Isoflurano/toxicidade , Fragmentos de Peptídeos/toxicidade , Proteínas tau/metabolismo , Animais , Apoptose/fisiologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Células PC12 , Fosforilação/efeitos dos fármacos , Fosforilação/fisiologia , RatosRESUMO
The effects of a single compound and a mixture of traditional Chinese medicine (TCM) on promoting proliferation, differentiation, and migration of neural stem cells and regulating their microenvironment have been observed by Chinese scholars in recent years. These results showed good prospects in improving neural regeneration and repair of neurological disorders such as ischemic brain injury, Alzheimer's disease, Parkinson's disease, and depression. According to the TCM theory, the relationship between life of an individual and the disease was regarded as an entirety, and the theory emphasized the treatment based on syndrome differentiation since ancient times. In this paper, we attempted to introduce these medicines, which belong to natural products and have already been proved to possess clear therapeutic action on human bodies in the clinical setting. We summarized their effects promoting brain neurogenesis and repairing brain injuries in animal models and some mechanisms at the cellular and molecular levels.
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Medicamentos de Ervas Chinesas/uso terapêutico , Regeneração Nervosa/efeitos dos fármacos , Doenças do Sistema Nervoso/tratamento farmacológico , Animais , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Medicina Tradicional Chinesa/métodos , Doenças do Sistema Nervoso/metabolismo , Doenças do Sistema Nervoso/terapia , Células-Tronco Neurais/efeitos dos fármacos , Células-Tronco Neurais/metabolismo , Células-Tronco Neurais/fisiologia , Neurogênese/efeitos dos fármacosRESUMO
The fast recombination of photogenerated charge carriers and poor stability have impeded the application of many narrow band gap semiconductors with otherwise excellent photocatalytic performance. A metal-semiconductor Schottky junction is a promising strategy to accelerate charge separation and enhance catalytic efficiency. However, the preparation of these structures often involves intricate processes and harsh conditions, which will inevitably destroy the electronic structures of the semiconductors and ruin their original properties in practical applications. In this study, a reduced graphene oxide (RGO)-enwrapped Cu-Cu2O nanocomposite (Cu-Cu2O@RGO) spontaneously evolved from an aqueous alcoholic solution containing cupric ions and graphene oxide (GO) under simulated sunlight irradiation. During this process, GO reduction and Cu-Cu2O nanoparticles growth occurred simultaneously in conjunction with in situ RGO encapsulation. Benefiting from the superior intrinsic semiconductor characteristic retention under mild reaction conditions, strong component interactions, and efficient interfacial charge transfer, the distinctive Cu-Cu2O@RGO nanocomposite supplied multiple channels for rapid electron transfer to substantially enhance the charge carrier separation efficiency and provide perfect chemical protection to effectively prevent Cu2O photocorrosion. This product also greatly suppressed self-aggregation to decrease the size of nanoparticles. Based on these merits, the Cu-Cu2O@RGO nanocomposite offered promising advances in photoelectrochemical and photocatalytic H2 evolution. This work provides an innovative photoinduced strategy for constructing an RGO-enwrapped semiconductor nanocomposite with efficient charge transfer interfaces while providing novel insights for the efficient solar energy utilization.
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Depressive disorders are devastating metal illness that can lead to deterioration in the social and occupational functioning of affected individuals. The etiology and pathophysiology of depression remain unknown. Present study was performed to better understand the underlying causes of depression. An experimental animal depression was induced in male BALB/c mice subjected to a chronic mild stress (CMS) procedure involving different stressor for consecutive 4 weeks. A cDNA microarray was employed to study the effects of CMS on the gene expression in cerebral cortex and hippocampus. 4-week CMS caused a significant reduction of 2% sucrose consumption. Morris water maze procedure showed impairment in cognitive function in stressed mice. Results of microarray showed that there were 102 and 60 genes were markedly affected by CMS treatment in cerebral cortex and hippocampus regions, respectively, including DNA damage/repair-related enzymes, anti-oxidant enzyme, and cyclin and cyclin-dependent kinase (CDK). These findings suggest that multiple biochemical effects play an important role the etiology of depression.
Assuntos
Córtex Cerebral/fisiologia , Perfilação da Expressão Gênica , Hipocampo/fisiologia , Análise de Sequência com Séries de Oligonucleotídeos , Estresse Fisiológico/fisiologia , Animais , Depressão/genética , Depressão/fisiopatologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular , Testes NeuropsicológicosRESUMO
AIM: To investigate the protective effects of octacosanol in 6-hydroxydopamine-induced Parkinsonian rats and find whether octacosanol has effects on pro nerve growth factor (pro-NGF), NGF and the downstream effector proteins. METHODS: Behavioral tests, enzymatic assay, tyrosine hydroxylase immunohistochemistry, TUNEL and Western blot were used to investigate the effects of octacosanol in this rat model of PD. RESULTS: Oral administration of octacosanol (35-70 mg/kg, po for 14 d) significantly improved the behavioral impairments in rats induced by 6-OHDA and dose-dependently preserved the free radical scavenging capability of the striatum. Octacosanol treatment also effectively ameliorated morphological appearances of TH-positive neuronal cells in nigrostriatal systems and decreased the apoptotic cells induced by 6-OHDA in striatum. In addition, octacosanol strikingly blocked the 6-OHDA-induced increased expression of proNGF-p75NTR-sortilin death signaling complex and its downstream effector proteins. Meantime, octacosanol prevented the decreased levels of NGF, its receptors TrkA and p-Akt which together mediated the cell survival pathway. CONCLUSION: The findings implicated that the anti-parkinsonism effects afforded by octacosanol might be mediated by its neuro-microenvironment improving potency through retrieving the ratios of proNGF:NGF and the respective receptors p75NTR:TrkA in vivo. Due to its excellent tolerability and non-toxicity, octacosanol may be a promising agent for PD treatment.
Assuntos
Antiparkinsonianos/farmacologia , Álcoois Graxos/farmacologia , Transtornos Parkinsonianos/tratamento farmacológico , Animais , Antiparkinsonianos/administração & dosagem , Antiparkinsonianos/toxicidade , Western Blotting , Relação Dose-Resposta a Droga , Álcoois Graxos/administração & dosagem , Álcoois Graxos/toxicidade , Masculino , Fator de Crescimento Neural/efeitos dos fármacos , Fator de Crescimento Neural/metabolismo , Fatores de Crescimento Neural/efeitos dos fármacos , Fatores de Crescimento Neural/metabolismo , Proteínas do Tecido Nervoso , Oxidopamina , Transtornos Parkinsonianos/fisiopatologia , Precursores de Proteínas/efeitos dos fármacos , Precursores de Proteínas/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Receptor trkA/metabolismo , Receptores de Fatores de Crescimento , Receptores de Fator de Crescimento Neural/metabolismoRESUMO
OBJECTIVE: To study the relationship between oxidative DNA damage and mitochondrial apoptosis relative proteins in rat striatum induced by 6-hydroxydopamine (6-OHDA) during the pathogenesis of Parkinson's disease (PD). METHODS: 6-OHDA was stereotactically injected into the bilateral right striatum of rats to produce PD models. Assays for 8-oxo-dG immunohistochemistry and Western blot for MTH1, Cytochrome c, Cl-caspase 9 and Cl-caspase 3 in right striatum was separately conducted. RESULTS: In 10 successful PD rats, compared with either sham or normal group, there were obvious more 8-oxo-dG positive cells in lesioned striatum while there was a lower expression of MTH1. Furthermore, the expressions of such intrinsic apoptotic pathway factors as cytoplasmic Cytochrome c, Cl-caspase 9 and Cl-caspase 3 were highly up-regulated in lesioned striatum. CONCLUSION: Oxidative DNA damage plays a key role in the pathogenesis of PD. Furthermore Cytochrome c, caspase 9 and caspase 3 are involved in the regulation of apoptosis under oxidative DNA damage induced by 6-OHDA.
Assuntos
Corpo Estriado/metabolismo , Dano ao DNA , Proteínas Mitocondriais/metabolismo , Oxidopamina/efeitos adversos , Doença de Parkinson/metabolismo , Animais , Apoptose , Caspase 3/metabolismo , Caspase 9/metabolismo , Citocromos c/metabolismo , Masculino , Doença de Parkinson/etiologia , Doença de Parkinson/patologia , Ratos , Ratos Sprague-DawleyRESUMO
Excitotoxicity is one of the most extensively studied processes of neuronal death and plays an important role in Alzheimer's disease. In the present study, the protective effects of Gossypium herbaceam extracts (GHE) on learning and memory impairment induced by excitatory neurotoxin ibotenic acid were examined in vivo using Morris water maze. Furthermore, neuroprotective effects of GHE were investigated with methods of immunohistochemistry and biochemistry. Our data showed that oral administration with GHE at the doses of 35, 70 and 140 mg/kg exerted an improved effect on the learning and memory impairment in rats induced by intracerebral injection of ibotenic acid. To confirm the precise mechanism of memory improvement by presence of GHE, we further investigated the potential protection on the hippocampus. Our findings suggest that GHE afforded a beneficial inhibition on pro-apoptosis proteins expression following ibotenic acid. Additionally, calcium pump activity and calbindin-D28k expression were dramatically increased after GHE treatment, implicating that the modulation of calcium homeostasis could be involved in the mechanism underlying neuroprotection of GHE against ibotenic acid-induced excitotoxicity. These data suggested that GHE could be a potential agent for preventing or retarding the development or progression of Alzheimer's disease.
Assuntos
Gossypium/química , Hipocampo/fisiopatologia , Síndromes Neurotóxicas/tratamento farmacológico , Fitoterapia/métodos , Preparações de Plantas/uso terapêutico , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Calbindina 1 , Calbindinas , ATPases Transportadoras de Cálcio/metabolismo , Caspase 3/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Reação de Fuga/efeitos dos fármacos , Agonistas de Aminoácidos Excitatórios/toxicidade , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Ácido Ibotênico/toxicidade , Injeções Intraventriculares/métodos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/metabolismo , Síndromes Neurotóxicas/fisiopatologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Sprague-Dawley , Proteína G de Ligação ao Cálcio S100/metabolismo , Fatores de Tempo , Proteína X Associada a bcl-2/metabolismoRESUMO
AIM: To apply 3.0 magnetic resonance imaging (MRI) to study the effects of long-term, low dose hormone replacement therapy (HRT) on the brain parenchyma of postmenopausal women. METHODS: A total of 155 postmenopausal healthy female medical staff members from Peking Union Medical College Hospital were enrolled. The HRT group was composed of 71 subjects who had been given a low dose of HRT for over 4 years, while 84 women who had never been given HRT were enrolled in the control group. The Mini-Mental State Examination (MMSE) was used to evaluate mental state, and an Enzyme-Linked ImmunoSorbent Assay (ELISA) was used to detect plasma levels of sex hormones. In addition, all participants were subjected to an MRI, including axial T2 weighted imaging (T2WI), fluid-attenuated inversion recovery (FLAIR), T1 weighted imaging (T1WI, oblique coronal, vertical to the hippocampus, slice thickness 3 mm without gaps), and a 3D image of the whole brain. RESULTS: The ELISA showed that the plasma level of estradiol in the HRT group was significantly higher than that in the control group (P<0.05). No differences were observed in the MMSE between the two groups. In participants older than 70 years of age, the number of deep white matter hyperintensities (DWMHs) in the control group was significantly higher than that in the HRT group (P=0.0013); however, in other age subgroups, no statistical differences were observed. Finally, no significant difference in periventricular hyperintensity (PVH) between the two groups was observed. CONCLUSION: We found that a high plasma level of estradiol in postmenopausal women receiving long-term HRT was correlated with the survival of brain parenchyma.Acta Pharmacologica Sinica (2009) 30: 1065-1070; doi: 10.1038/aps.2009.81.
Assuntos
Encéfalo , Terapia de Reposição Hormonal , Imageamento por Ressonância Magnética , Idoso , Idoso de 80 Anos ou mais , Animais , Encéfalo/anatomia & histologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Estradiol/sangue , Estradiol/farmacologia , Feminino , Humanos , Entrevista Psiquiátrica Padronizada , Pessoa de Meia-IdadeRESUMO
Amyloid-beta (Abeta) is considered to be responsible for the pathogenesis of Alzheimer's disease. In the present study, the protective effect of Gossypium herbaceam extracts (GHE) on learning and memory impairment induced by Abeta were examined in vivo using Morris water maze and step through task. Furthermore, the antioxidant activity and neuroprotective effect of GHE was investigated with methods of histochemistry and biochemistry. These data showed that oral administration with GHE at the doses of 35, 70 and 140 mg/kg exerted an improved effect on the learning and memory impairment in rats induced by intracerebroventricular (i.c.v.) injection of 10 microg of Abeta(25-35). Subsequently, the GHE afforded a beneficial action on promotion on the activity of glutathione peroxidase and catalase, as well as inhibition on the NF-kappaB activation in the hippocampus followed by the presence of Abeta(25-35). Meanwhile, the number of degenerating neurons with an apoptotic feature was dramatically decreased in hippocampus after treatment with GHE, implicating that its antioxidant stress and inhibition of NF-kappaB activation could be involved in the mechanism underlying neuroprotection of GHE against Abeta-induced cell death. These findings suggested that GHE might be a potential agent for treatment of Alzheimer's disease.
Assuntos
Precursor de Proteína beta-Amiloide/metabolismo , Gossypium , Hipocampo/metabolismo , Hipocampo/patologia , Transtornos da Memória/metabolismo , Transtornos da Memória/prevenção & controle , NF-kappa B/antagonistas & inibidores , Degeneração Neural/patologia , Degeneração Neural/terapia , Fitoterapia , Percepção Espacial , Animais , Cromatografia Líquida de Alta Pressão , Imuno-Histoquímica , Masculino , Aprendizagem em Labirinto , Degeneração Neural/metabolismo , Extratos Vegetais , Ratos , Ratos Sprague-DawleyRESUMO
The effects of long-term low-dose hormone replacement therapy (HRT) on the level of hormone in plasma and on the binding capacity of peripheral-type benzodiazepine receptor (PBR) on the platelet membranes were investigated among women. This study was a retrospective and case-controlled study where 64 women using long-term low-dose HRT for over 4 years entered the study and 99 women, age and education matched, were enrolled as control. Plasma hormone level and platelet PBR binding capacity of two groups were analyzed. A significant increase in plasma estradiol level in women using HRT was observed, compared to those in the control group. Meanwhile, women in the HRT group displayed higher platelet PBR binding capacity. Further analysis demonstrated that the binding capacity of platelet PBR was closely related to estradiol plasma level in all subjects. These results suggest that long-term low-dose HRT could relieve the decrease of estradiol level in plasma and PBR binding capacity on platelets in postmenopausal women, alleviate the endocrine imbalance process, and might be beneficial for reducing the risks of some diseases.
Assuntos
Plaquetas/metabolismo , Estradiol/sangue , Terapia de Reposição de Estrogênios/métodos , Pós-Menopausa/metabolismo , Receptores de GABA/sangue , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Isoquinolinas/metabolismo , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , TrítioRESUMO
To determine the survival and differentiation of cultured Human amniotic cells (HACs) upon transplantation into the brain of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson disease (PD) mice. Mouse model of PD was established with injections of MPTP (15 mg/kg, fourth, 2 h interval). After being labeled with PKH26, HACs isolated from human were transplanted into the striatum of PD mice. Immunohistochemistry was performed to evaluate the toxicity of MPTP in the substantia nigra, graft survival and endogenous neurogenesis. Brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) level in the striatum were tested by ELISA. Our results showed that cultured HACs can express the marker of neural progenitor cells and differentiate into neuron, dopaminergic neuron, astrocyte and oligodendrocyte. TH-positive neural cells were significantly reduced in the substantia nigra in the model mice, whereas which increased in transplantation mice. Immunohistology results showed that transplanted HACs survived and migrated in the brain of PD model mouse, though no morphological integration was observed. BrdU-positive cells in the Subventricular zone (SVZ) and neurotrophins of the striatum increased in the transplantation mice. The results suggested that transplanted HACs could survive and promote the endogenous neurogenesis of mice, which maybe related to the increased level of neurotrophins of the striatum.