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1.
J Vis Exp ; (155)2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32065164

RESUMO

Rheumatoid arthritis (RA) is a complex chronic inflammatory autoimmune disease. The pathogenesis of the disease is related to invariant natural killer T (iNKT) cells. Patients with active RA present fewer iNKT cells, defective cell function, and excessive polarization of Th1. In this study, an RA animal model was established using a mixture of hGPI325-339 and hGPI469-483 peptides. The iNKT cells were obtained by in vivo induction and in vitro purification, followed by infusion into RA mice for adoptive immunotherapy. The in vivo imaging system (IVIS) tracking revealed that iNKT cells were mainly distributed in the spleen and liver. On day 12 after cell therapy, the disease progression slowed down significantly, the clinical symptoms were alleviated, the abundance of iNKT cells in the thymus increased, the proportion of iNKT1 in the thymus decreased, and the levels of TNF-α, IFN-γ, and IL-6 in the serum decreased. Adoptive immunotherapy of iNKT cells restored the balance of immune cells and corrected the excessive inflammation of the body.

2.
Hemoglobin ; : 1-3, 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31985312

RESUMO

We report a novel mutation on the ß-globin gene in a female of the Chinese population. This mutation produces a ß-globin variant that can be detected by the capillary electrophoresis (CE) method, but coelutes with Hb A2 by high performance liquid chromatography (HPLC). DNA sequencing showed a mutation of codon 46 and it was named Hb Cenxi [ß46(CD5)Gly→Arg (GGG>CGG), HBB: c.139G>C] for the city of birth of the proband. She presented normal hematological parameters.

3.
Stem Cell Res ; 42: 101687, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31869684

RESUMO

The human induced pluripotent stem cell (iPSC) line YAHKMUi001-A was derived from the dermal fibroblasts of a patient with Tetralogy of Fallot (TOF), with a mutation in the TBX1 gene (c.928G > A). The skin fibroblasts were obtained from a 4-year-old boy, and were infected with Sendai virus expressing the Yamanaka factors. The YAHKMUi001-A iPSC line expresses pluripotent stem cell markers, displays a normal karyotype, and has the capacity to differentiate into 3 germ layers. This cell line model can be a good tool to study the pathological mechanism of the TBX1 gene mutations associated with TOF.

4.
Sensors (Basel) ; 19(23)2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31757038

RESUMO

Abstract: The positioning technology to find shallow underground vibration sources based on a wireless sensor network is receiving great interest in the field of underground position measurements. The slow peaking and strong multi-waveform aliasing typical of the underground vibration signal result in a low extraction accuracy of the time difference and a poor source-positioning accuracy. At the same time, the transmission of large amounts of sensor data and the host computer's slow data processing speed make locating a source a slow process. To address the above problems, this paper proposes a method for high-precision time-difference measurements in near-field blasting and a method for its hardware implementation. First, based on the broadband that is typical of blast waves, the peak frequency of the P-wave was obtained in the time-frequency domain, taking advantage of the difference in the propagation speed of the P-wave, S-wave, and the surface wave. Second, the phase difference between two sensor nodes was found by means of a spectral decomposition and a correlation measurement. Third, the phase ambiguity was eliminated using the time interval of the first break and the dynamic characteristics of the sensors. Finally, following a top-down design idea, the hardware system was designed using Field Programmable Gate Array(FPGA). Verification, using both numerical simulations and experiments, suggested that compared with generalized cross-correlation-based time-difference measurement methods, the proposed method produced a higher time-difference resolution and accuracy. Compared with the traditional host computer post-position positioning method, the proposed method was significantly quicker. It can be seen that the proposed method provides a new solution for solving high-precision and quick source-location problems, and affords a technical means for developing high-speed, real-time source-location instruments.

5.
Int Immunopharmacol ; 77: 105948, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31629216

RESUMO

OBJECTIVE: The role of iNKT cells was investigated in chronic adipose tissue inflammation in obese mice after administration of α-GalCer in different pathways. METHODS: C57BL/6J mice were fed high-fat diet (HFD) for 12 weeks to establish the obese mouse model. The pathology of adipose tissue was observed by H&E staining. The rates of iNKT cells, macrophages and cell subsets in adipose tissue were detected by FCM. Cytokine levels in serum and adipose tissue lymphocyte-stimulated supernatants were assessed with the CBA kit. The expression levels of related transcription factor in adipose tissue were detected by Western blot. RESULTS: The proportions of iNKT cells, iNKT10 cells and M2 macrophages were decreased, while those of iNKT1 and M1 macrophages were increased in adipose tissue of HFD-fed mice. The expression levels of the related transcriptional proteins E4BP4 and Arg-1 were decreased while iNOS expression was increased in adipose tissue. Administration of α-GalCer by subcutaneous injection resulted in increased rates of iNKT10 cells and M2 macrophages, and decreased amounts of M1 macrophages in adipose tissue of HFD-fed mice. The expression of E4BP4 and Arg-1 were up-regulated, but iNOS was down-regulated. Meanwhile, infiltration of inflammatory cells into adipose tissue was further reduced. CONCLUSION: The imbalance between the proportions of iNKT1 and iNKT10 cells may be involved in the development of chronic inflammation in obese adipose tissue. Administration of α-GalCer by subcutaneous injection in HFD-fed mice activates adipose tissue iNKT10 cells, which promote M2 macrophage polarization and improve chronic inflammation in obese adipose tissue.

6.
Immunogenetics ; 71(7): 489-499, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31297569

RESUMO

Epigenetic modifications have been shown to be important for immune cell differentiation by regulating gene transcription. However, the role and mechanism of histone methylation in the development and differentiation of iNKT cells in rheumatoid arthritis (RA) mice have yet to be deciphered. The DBA/1 mouse RA model was established by using a modified GPI mixed peptide. We demonstrated that total peripheral blood, thymus, and spleen iNKT cells in RA mice decreased significantly, while iNKT1 in the thymus and spleen was increased significantly. PLZF protein and PLZF mRNA levels were significantly decreased in thymus DP T cells, while T-bet protein and mRNA were significantly increased in thymus iNKT cells. We found a marked accumulation in H3K27me3 around the promoter regions of the signature gene Zbtb16 in RA mice thymus DP T cells, and an accumulation of H3K4me3 around the promoters of the Tbx21 gene in iNKT cells. The expression levels of UTX in the thymus of RA mice were significantly reduced. The changes in the above indicators were particularly significant in the progressive phase of inflammation (11 days after modeling) and the peak phase of inflammation (14 days after modeling) in RA mice. Developmental and differentiation defects of iNKT cells in RA mice were associated with abnormal methylation levels (H3K27me3 and H3K4me3) in the promoters of key genes Zbtb16 (encoding PLZF) and Tbx21 (encoding T-bet). Decreased UTX of thymus histone demethylase levels resulted in the accumulation of H3K27me3 modification.


Assuntos
Artrite Reumatoide/patologia , Lisina/metabolismo , Células T Matadoras Naturais/patologia , Regiões Promotoras Genéticas , Timo/fisiologia , Animais , Artrite Experimental/patologia , Diferenciação Celular , Epigênese Genética , Regulação da Expressão Gênica , Histona Desmetilases/genética , Histona Desmetilases/metabolismo , Metilação , Camundongos Endogâmicos DBA , Proteína com Dedos de Zinco da Leucemia Promielocítica/genética , Proteína com Dedos de Zinco da Leucemia Promielocítica/metabolismo , Baço/patologia , Proteínas com Domínio T/genética , Proteínas com Domínio T/metabolismo
7.
Int Immunopharmacol ; 74: 105727, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31284229

RESUMO

The existence of association between the subpopulation of iNKT cells with different functions and nonalcoholic fatty liver disease has not been confirmed. To investigative the role of iNKT cells in the pathogenesis of nonalcoholic fatty liver disease, we established a non-alcoholic fatty liver model by feeding C57BL/6J mice for 12 weeks with a high-fat diet and injecting α-GalCer through different routes to activate hepatic iNKT cells. The liver of the mice fed a high-fat diet (HFD) had severe hepatic steatosis appearance, elevated pro-inflammatory cytokines and reduced anti-inflammatory cytokines in the liver, and high serum levels of TC, LDL, HDL, and ALT. Our results showed that the percentage of iNKT cells in the liver of the HFD-fed mice was lower than that of the control mice. The expression levels of the related transcription factor of T-bet increased but that of GATA-3 decreased in the HFD-fed mice. The administration of α-GalCer by intraperitoneal injection resulted in increasing of hepatic iNKT and iNKT2 cells but decreasing of hepatic iNKT1 cells, and the expression of GATA-3 and anti-inflammatory cytokine (IL-4) was increased in the liver, and hepatic steatosis was ameliorated in the HFD-fed mice. The administration of α-GalCer by subcutaneous injection resulted in a decrease in hepatic iNKT and iNKT2 and an augmentation of hepatic iNKT1 cells. However, hepatic steatosis was not significantly improved. We concluded that the intraperitoneal injection with α-GalCer effectively improved hepatic steatosis, according to increasing the number of hepatic iNKT2 cells. The precise mechanism requires further exploration.

8.
Neural Regen Res ; 14(8): 1438-1444, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30964070

RESUMO

Genome-wide studies have reported that Parkinson's disease is associated with abnormal expression of various growth factors. In this study, male C57BL/6 mice aged 10 weeks were used to establish Parkinson's disease models using an intraperitoneal injection of 60 mg/kg 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. 28 days later, 10 or 100 ng fibroblast growth factor 20 was injected intracerebroventricularly. The electrophysiological changes in the mouse hippocampus were recorded using a full-cell patch clamp. Expression of Kv4.2 in the substantia nigra was analyzed using a western blot assay. Serum malondialdehyde levels were analyzed by enzyme-linked immunosorbent assay. The motor coordination of mice was evaluated using the rotarod test. The results showed that fibroblast growth factor 20 decreased A-type potassium current in neurons of the substantia nigra, increased long-term potentiation amplitude in the hippocampus, and downregulated Kv4.2 expression. A high dose of fibroblast growth factor 20 reduced serum malondialdehyde levels and enhanced the motor coordination of mice. These findings confirm that fibroblast growth factor 20 has a therapeutic effect on the toxicity induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, and its mechanism of action is associated with the inhibition of A-type K+ currents and Kv4.2 expression. All animal procedures were approved by the Animal Care and Use Committee of Qilu Hospital of Shandong University, China in 2017 (approval No. KYLL-2017-0012).

9.
J Cancer Res Clin Oncol ; 145(5): 1133-1146, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30805774

RESUMO

PURPOSE: Human mesenchymal stem cells (hMSCs) have been applied in a variety of therapies recently. However, the role of MSCs in tumor progression remains largely elusive. Some studies demonstrated that MSCs can promote tumor growth, while others had opposite results. Therefore, the lack of evidence about the effect of MSCs on tumor cells impedes its further use. METHODS: In the current study, hMSCs from amniotic membrane (hAMSCs) and umbilical cord (hUCMSCs) were used to evaluate the effects of MSCs on tumor development in vitro and in vivo. Two different animal models based on subcutaneous xenograft bearing nude mice and a murine experimental metastatic model were established for in vivo study. Moreover, cytokines regulated by MSCs co-cultured with cancer cells SPC-A-1 were also analyzed by cytokine array. RESULTS: Our results indicated that hUCMSCs not only did not promote proliferation in cancer cells, but also inhibited migration. In addition, they inhibited tube formation in human umbilical vein endothelial cells (HUVECs). Although hAMSCs also showed inhibitory effects on cancer cell motility, the proliferation of cancer cells was indeed enhanced. The in vivo data revealed that hUCMSCs did not promote tumor progression in lung adenocarcinoma and gastric carcinoma xenografts. Nevertheless, hAMSCs could do. The results from murine experimental metastatic model also demonstrated that neither hUCMSCs nor hAMSCs significantly enhanced the lung metastasis. The data from cytokine array showed that 11 inflammatory factors, 8 growth factors and 11 chemokines were remarkably secreted and changed. CONCLUSIONS: In view of the data from in vitro and in vivo studies, the exploitation of hUCMSCs in new therapeutic strategies should be safe compared to hAMSCs under malignant conditions. Moreover, this is the first report to systematically elucidate the possible molecular mechanisms involved in UCMSC- and AMSC-affected tumor growth and metastasis.


Assuntos
Âmnio/citologia , Comunicação Celular , Transformação Celular Neoplásica/metabolismo , Células-Tronco Mesenquimais/metabolismo , Cordão Umbilical/citologia , Animais , Biomarcadores , Diferenciação Celular , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Técnicas de Cocultura , Meios de Cultivo Condicionados , Citocinas/metabolismo , Modelos Animais de Doenças , Xenoenxertos , Células Endoteliais da Veia Umbilical Humana , Humanos , Imunofenotipagem , Células-Tronco Mesenquimais/citologia , Camundongos , Metástase Neoplásica
10.
Food Chem ; 277: 674-681, 2019 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-30502202

RESUMO

In this study, the capacity of asymmetrical flow field-flow fractionation (AF4) coupled with multiangle light scattering (MALS) and differential refractive index (dRI) detectors, to monitor starch retrogradation behavior in situ was evaluated. Meanwhile, the starch samples were characterized by differential scanning calorimetry (DSC) and fourier transform infrared spectroscopy (FTIR). The effect of the botanical origin, amylose/amylopectin ratio, storage conditions (i.e., temperature and time), and salt on starch retrogradation was systematically investigated. The starch aggregation and disassociation is a kinetic equilibrium process that is dependent on the storage conditions and the content of amylose. Moreover, it was found that nitrate ions retarded starch retrogradation behavior by inhibiting the formation of hydrogen bonds between amylose molecules. The results suggest that the formation of the small amylose aggregates plays an important role in starch retrogradation and maize amylopectin degradation. The information obtained by AF4-MALS-dRI is valuable for understanding the starch retrogradation mechanism.


Assuntos
Fracionamento por Campo e Fluxo/métodos , Amido/química , Amilopectina/análise , Amilose/análise , Varredura Diferencial de Calorimetria , Difusão Dinâmica da Luz , Ligações de Hidrogênio , Nitratos/química , Refratometria , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura Ambiente , Zea mays/química , Zea mays/metabolismo
11.
Nanotechnology ; 30(1): 015402, 2019 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-30362462

RESUMO

Solar steam generation provides a renewable and environmentally friendly approach to solve the water shortage issue. The pursuit of efficient, stable, and cheap photothermal agents is thus of great significance. In this work, Cu nanoparticles (NPs) fabricated simply by a substitution reaction, exhibit a near-unity (∼97.7%) light absorption, covering a broad incident angle and wavelength range (200-1300 nm). Thereby, a high photothermal conversion efficiency of 93% is achieved. The excellent photothermal performance offers a unique opportunity for the development of solar steam generation. By coating the Cu NPs on a cellulose membrane, a solar steam generation efficiency up to 73% is acquired at a low irradiation power density of 2 kW m-2 (1 kW m-2 = 1 sun). Moreover, the Cu NPs are recyclable with the high stability being resistant to heat, photoirradiation and corrosion of brine.

12.
Int Immunopharmacol ; 67: 427-440, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30586666

RESUMO

BACKGROUND: The therapeutic effect of adoptive infusion of specific thymus-derived invariant natural killer T (iNKT) cells in a mouse model of rheumatoid arthritis (RA) was observed, and the mechanism of cellular immunotherapy was preliminarily explored. METHODS: Thymus-derived iNKT cells were infused to RA model mice, with α-GalCer as a positive control. Then, ankle swelling was examined, as well as inflammatory cell infiltration to the joint tissue (hematoxylin-eosin [H&E] staining). Flow cytometry (FCM) was used to assess iNKT cell and helper T lymphocyte (Th) subsets. Serum cytokine levels were determined with cytometric bead array (CBA), with protein expression levels of related transcription factors assessed by Western blot. RESULTS: The joint swelling in RA model animals were significantly improved in the cell therapy and α-GalCer positive control groups (P < 0.05). In addition, iNKT frequencies in peripheral blood, the thymus and spleen were increased significantly (P < 0.05). Meanwhile, iNKT1 subset frequencies in the thymus and spleen were decreased, as well as splenic Th1 and Th17 cell subset rates, and serum TNF-α, IFN-γ and IL-6 levels. The rates of iNKT2 and Th2 subsets as well as IL-4 and IL-10 levels were increased (P < 0.05). Thymus GATA-3 and splenic PLZF protein levels were increased (P < 0.05). CONCLUSIONS: Adoptive infusion of thymus-derived iNKT cells exerts therapeutic effects in RA mice by increasing iNKT frequency, altering the proportions of iNKT cell subsets, correcting Th cell subset imbalance and reducing the amounts of inflammatory cytokines.


Assuntos
Artrite Reumatoide/terapia , Imunoterapia Adotiva , Células T Matadoras Naturais , Timo/citologia , Animais , Artrite Reumatoide/induzido quimicamente , Masculino , Camundongos , Células T Matadoras Naturais/classificação , Peptídeos/toxicidade , Distribuição Aleatória , Baço/citologia
13.
Zhongguo Yi Liao Qi Xie Za Zhi ; 42(6): 444-445, 2018 Nov 30.
Artigo em Chinês | MEDLINE | ID: mdl-30560627

RESUMO

In Nov.2017, Shanghai CFDA began to pilot medical device registrant project in China. This project is a bold attempt to medical device supervision. And it's quite helpful for promoting innovation and development of medical devices in Shanghai. However, the "R&D-Production-separate" characteristic enhances risks in medical device life-cycle. It also brings more challenges to registrant on medical device risk management. In order to protect interested parties fully and effectively, we will discuss why registrants need to manage risk and what they should pay attention to in this article.


Assuntos
Equipamentos e Provisões , Gestão de Riscos , China , Sistema de Registros
14.
Free Radic Res ; 52(9): 961-969, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30422023

RESUMO

Emerging evidence suggests that microbial pathogens may induce oxidative stress in infected hosts. The aim of the present study was to investigate the relationship between changes in oxidative stress and intestinal infection with and without antibiotic treatment in animal models. Sprague-Dawley (SD) rats were divided into three groups: rats infected with Salmonella enterica serovar Enteritidis (S. enteritidis), rats infected with S. enteritidis followed by norfloxacin treatment, and the control group. To evaluate oxidative stress changes, levels of 8-oxo-7,8-dihydroguanosine (8-oxo-Gsn) and 8-oxo-7,8-dihydro-2-deoxyguanosine (8-oxo-dGsn), which represented oxidative damage to RNA and DNA, respectively, were analysed in urine and tissue samples. In urine, the level of 8-oxo-Gsn increased significantly after oral exposure to S. enteritidis (p ≤ 0.001) and returned to baseline after recovery. Notably, norfloxacin treatment decreased the level of 8-oxo-Gsn in urine significantly (p = 0.001). Changes of 8-oxo-Gsn measured in tissues from the small intestine, colon, liver and spleen were consistent with 8-oxo-Gsn measured in urine. Our study suggested that 8-oxo-Gsn in urine may serve as a highly sensitive biomarker for evaluating the severity of S. enteritidis infection and the effectiveness of antibiotic treatment against infection.


Assuntos
Dano ao DNA/efeitos dos fármacos , Fígado/metabolismo , Estresse Oxidativo , Animais , Dano ao DNA/genética , Humanos , /patologia , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Fígado/microbiologia , Fígado/patologia , Oxirredução , Valor Preditivo dos Testes , RNA/química , Ratos , Salmonella enteritidis/patogenicidade
15.
Sheng Li Xue Bao ; 70(5): 571-578, 2018 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-30377697

RESUMO

APP/PS1/tau triple transgenic (3xTg) mouse is a classical animal model of Alzheimer's disease (AD), which has abnormalities in recognition and electrophysiological properties at early 6-month-old age. However, few studies were performed by using simultaneously recording cognitive behavior and brain electrical activity in the conscious 3xTg mice. By using a new wireless recording system, we recorded hippocampal Theta oscillations in 3xTg mice during the process of fear conditioning test. The results showed that: (1) in training session, no significant difference in the fear behavior and hippocampal Theta activity was found between 3xTg mice and WT mice; (2) in test session, 3xTg mice showed a significant decrease in freezing ratio compared with WT mice when they were exposed to conditioning stimulus (CS); (3) the 3xTg mice showed lower peak power in Theta oscillation in both Pre-CS and CS duration compared with WT mice; (4) CS effectively induced an increase in the peak frequency of Theta oscillation in WT mice, but not in 3xTg mice. These results indicated that the impairment of cognition behavior in 3xTg mice was accompanied with the decreased peak power and peak frequency of Theta oscillation in the hippocampus, suggesting that a decline in Theta oscillation might be involved in the impairments of the fear conditioning, and the enhanced hippocampal Theta oscillation may be beneficial for improving AD cognitive function.


Assuntos
Doença de Alzheimer/fisiopatologia , Condicionamento Clássico , Medo , Ritmo Teta , Tecnologia sem Fio , Animais , Cognição , Modelos Animais de Doenças , Hipocampo/fisiopatologia , Camundongos , Camundongos Transgênicos
16.
Brain Res Bull ; 143: 116-122, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30366065

RESUMO

Amyloid-ß (Aß) peptide and α-synuclein (α-syn) are major components of senile plaques in Alzheimer's disease (AD) and Lewy bodies in Parkinson's disease (PD), respectively. Co-occurrence of Aß and α-syn in the senile brains of AD and LB diseases suggests interactions between the two proteins. However, the significance of the overlapping deposition, especially the effects of α-syn on the Aß aggregation, still remains to be clarified. In the present study, we investigated the effects of α-syn pre-formed fibrils (PFFs) injection on the cognitive behaviors and Aß deposition in the brain of APP/PS1 transgenic AD mice by using Morris water maze (MWM) test, immunohistochemistry and western blot techniques. We found that APP/PS1 transgenic mice exhibited an obvious elevation in the α-syn load, as well as Aß deposition in the brain compared with wild type of C57 BL littermates. 5 months after cerebral injection of exogenous α-syn, MWM tests showed an alleviation in cognitive impairments in APP/PS1 mice; western blot and immunohistochemistry experiments also exhibited a significant reduction in Aß level in the brain of APP/PS1 mice injected with α-syn. These results suggest that α-syn aggregated in the brain of AD may act as a protective factor and defend the brain tissue from early Aß deposition and cognitive deficits.


Assuntos
Memória Espacial/efeitos dos fármacos , alfa-Sinucleína/farmacologia , Doença de Alzheimer/fisiopatologia , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Encéfalo/metabolismo , Transtornos Cognitivos/metabolismo , Disfunção Cognitiva/metabolismo , Modelos Animais de Doenças , Humanos , Masculino , Aprendizagem em Labirinto , Transtornos da Memória/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Placa Amiloide , Presenilina-1/metabolismo , Agregação Patológica de Proteínas
17.
Neurosci Bull ; 34(5): 736-746, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30099679

RESUMO

Alzheimer's disease (AD) is the most common form of dementia among the elderly, characterized by amyloid plaques, neurofibrillary tangles, and neuroinflammation in the brain, as well as impaired cognitive behaviors. A sex difference in the prevalence of AD has been noted, while sex differences in the cerebral pathology and relevant molecular mechanisms are not well clarified. In the present study, we systematically investigated the sex differences in pathological characteristics and cognitive behavior in 12-month-old male and female APP/PS1/tau triple-transgenic AD mice (3×Tg-AD mice) and examined the molecular mechanisms. We found that female 3×Tg-AD mice displayed more prominent amyloid plaques, neurofibrillary tangles, neuroinflammation, and spatial cognitive deficits than male 3×Tg-AD mice. Furthermore, the expression levels of hippocampal protein kinase A-cAMP response element-binding protein (PKA-CREB) and p38-mitogen-activated protein kinases (MAPK) also showed sex difference in the AD mice, with a significant increase in the levels of p-PKA/p-CREB and a decrease in the p-p38 in female, but not male, 3×Tg-AD mice. We suggest that an estrogen deficiency-induced PKA-CREB-MAPK signaling disorder in 12-month-old female 3×Tg-AD mice might be involved in the serious pathological and cognitive damage in these mice. Therefore, sex differences should be taken into account in investigating AD biomarkers and related target molecules, and estrogen supplementation or PKA-CREB-MAPK stabilization could be beneficial in relieving the pathological damage in AD and improving the cognitive behavior of reproductively-senescent females.


Assuntos
Doença de Alzheimer/patologia , Doença de Alzheimer/psicologia , Caracteres Sexuais , Doença de Alzheimer/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Modelos Animais de Doenças , Feminino , Hipocampo/metabolismo , Hipocampo/patologia , Humanos , Inflamação/metabolismo , Inflamação/patologia , Inflamação/psicologia , Masculino , Aprendizagem em Labirinto/fisiologia , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Emaranhados Neurofibrilares/metabolismo , Emaranhados Neurofibrilares/patologia , Placa Amiloide/metabolismo , Placa Amiloide/patologia , Placa Amiloide/psicologia , Presenilina-1/genética , Presenilina-1/metabolismo , Memória Espacial/fisiologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Proteínas tau/genética , Proteínas tau/metabolismo
18.
BMC Cancer ; 18(1): 833, 2018 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-30126367

RESUMO

BACKGROUND: The aim of this study was to evaluate the early anti-tumor efficiency of different therapeutic agents with a combination of multi-b-value DWI, DCE-MRI and texture analysis. METHODS: Eighteen 4 T1 homograft tumor models were divided into control, paclitaxel monotherapy and paclitaxel and bevacizumab combination therapy groups (n = 6) that underwent multi-b-value DWI, DCE-MRI and texture analysis before and 15 days after treatment. RESULTS: After treatment, the tumors in the control group were significantly larger than those in the combination group (P = 0.018). In multi-b-value DWI, the ADCslow obviously increased in the combination group compared to that in the others (P < 0.01). The f increased in the control and paclitaxel groups, but the combination group showed a significant decrease versus the others (P < 0.02). Additionally, in DCE-MRI, the decreasing Ktrans showed an evident difference between the combination and control groups (P = 0.003) due to the latter's increasing Ktrans. The intra-group comparisons of tumor texture in pre-, mid- and post-treatments showed that the entropy had all significantly increased in all groups (P < 0.01, SSF = 0-6), though the MPP, mean and SD increased only in the combination group (PMPP,mean,SD < 0.05, SSF = 4-6). Moreover, the inter-group comparisons revealed that the mean and MPP exhibited significant differences after treatment (Pmean,MPP < 0.05, SSF = 0-3). CONCLUSION: All these results suggest some strong correlations among DWI, DCE and texture analysis, which are beneficial for further study and clinical research.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Imagem de Difusão por Ressonância Magnética/métodos , Neoplasias Mamárias Animais/diagnóstico por imagem , Neoplasias Mamárias Animais/tratamento farmacológico , Aloenxertos , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bevacizumab/administração & dosagem , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Meios de Contraste/uso terapêutico , Modelos Animais de Doenças , Feminino , Humanos , Neoplasias Mamárias Animais/patologia , Camundongos , Paclitaxel/administração & dosagem , Resultado do Tratamento
19.
Sheng Li Xue Bao ; 70(3): 217-227, 2018 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-29926062

RESUMO

The specific loss of cholinergic neurons and the progressive deficits of cognitive function are the most primary characteristics of Alzheimer's disease (AD). Although the neurotoxicity of amyloid ß protein (Aß) in AD has been investigated extensively, it is still unclear whether the Aß aggregated in the medial septum (MS), a major cholinergic nucleus projecting to the hippocampus, could affect hippocampal synaptic plasticity and further impair the memory behaviors. The present study investigated the effects of Aß injection into the MS on hippocampal long-term potentiation (LTP) and cognitive behaviors of rats by using Morris water maze (MWM), Y maze and in vivo hippocampal LTP recording. The effects of kainic acid (KA), an agent with specific neurotoxicity to GABAergic neurons, were also observed. The results showed that: (1) Intra-MS injection of Aß25-35, not KA, impaired spatial learning and memory of rats in classical and reversal MWM tests; (2) Both Aß25-35 and KA impaired novelty-seeking behavior of rats in Y maze; (3) Intra-MS injection of Aß25-35, not KA, suppressed in vivo hippocampal LTP in the CA1 region of rats; (4) Both Aß25-35 and KA did not affect the motor ability in behavioral tests and the hippocampal paired-pulse facilitation (PPF) in electrophysiological recording. These results indicate that intra-MS injection of Aß could impair spatial memory, cognitive flexibility and exploratory motivation, as well as hippocampal LTP in rats, suggesting that the cholinergic neurons in the MS and the septo-hippocampal projection could be important targets of neurotoxic Aß, and the specific damage of cholinergic neurons in the MS is likely responsible for the impairments of hippocampal synaptic plasticity and cognitive function in AD.


Assuntos
Peptídeos beta-Amiloides/efeitos adversos , Cognição , Hipocampo/fisiopatologia , Potenciação de Longa Duração , Fragmentos de Peptídeos/efeitos adversos , Doença de Alzheimer , Animais , Ácido Caínico/efeitos adversos , Aprendizagem em Labirinto , Transtornos da Memória , Plasticidade Neuronal , Ratos , Aprendizagem Espacial , Memória Espacial
20.
Neurosci Biobehav Rev ; 92: 402-416, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29751052

RESUMO

This meta-analytical review examines whether a deletion variant in ADRA2B, a gene that encodes α2B adrenoceptor in the regulation of norepinephrine availability, influences cognitive processing of emotional information in human observers. Using a multilevel modeling approach, this meta-analysis of 16 published studies with a total of 2752 participants showed that ADRA2B deletion variant was significantly associated with enhanced perceptual and cognitive task performance for emotional stimuli. In contrast, this genetic effect did not manifest in overall task performance when non-emotional content was used. Furthermore, various study-level factors, such as targeted cognitive processes (memory vs. attention/perception) and task procedures (recall vs. recognition), could moderate the size of this genetic effect. Overall, with increased statistical power and standardized analytical procedures, this meta-analysis has established the contributions of ADRA2B to the interactions between emotion and cognition, adding to the growing literature on individual differences in attention, perception, and memory for emotional information in the general population.


Assuntos
Cognição/fisiologia , Emoções/fisiologia , Deleção de Genes , Memória/fisiologia , Receptores Adrenérgicos alfa 2/genética , Variação Genética , Humanos , Receptores Adrenérgicos alfa 2/deficiência
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