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1.
Acad Radiol ; 2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-33504445

RESUMO

RATIONALE AND OBJECTIVES: The purpose of this study was to explore conventional MRI features that can accurately differentiate central nervous system embryonal tumor, not otherwise specified (CNS ETNOS) from glioblastoma (GBM) in adults. MATERIALS AND METHODS: Preoperative conventional MRI images of 30 CNS ETNOS and 98 GBMs were analyzed by neuroradiologists retrospectively to identify valuable MRI features. Five blinded neuroradiologists independently reviewed all these MRI images, and scored MRI features on a five-point scale. Kendall's coefficient of concordance was used to measure inter-rater agreement. Diagnostic value was assessed by the area under the curve (AUC) of receiver operating curve, and sensitivity and specificity were also calculated. RESULTS: Seven MRI features, including isointensity on T1WI, T2WI, and FLAIR, ill-defined margin, severe peritumoral edema, ring enhancement, and broad-based attachment sign, were helpful for the differential diagnosis of these two entities. Among these features, ring enhancement showed the highest inter-rater concordance (0.80). Ring enhancement showed the highest AUC value (0.79), followed by severe peritumoral edema (0.67). The combination of seven features showed the highest AUC value (0.86), followed by that of three features (ill-defined margin, severe peritumoral edema, and ring enhancement) (0.83). CONCLUSION: Enhancement pattern, peritumoral edema, and margin are valuable for the discrimination between CNS ETNOS and GBM in adults.

2.
Int J Clin Exp Pathol ; 12(5): 1609-1617, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31933978

RESUMO

BACKGROUND: Choriocarcinoma is the most aggressive gestational trophoblastic disease, with massive local trophoblast invasion and vascular percolation, resulting in multiple organ metastases. Recent evidence has shown that long noncoding RNAs (lncRNAs) play an important role in tumor progression. This study aimed to investigate the expression and role of lncRNA PCA3 in the progression of choriocarcinoma. METHODS: First, the expression of lncRNA PCA3 in choriocarcinoma cells was detected using quantitative real-time PCR (qRT-PCR). Then functional assays such as cell proliferation assay, wound healing assay, and invasion assay were conducted to determine the role of PCA3. In addition, the specific molecular mechanism was studied using western blot, luciferase assay, and rescue experiment. RESULTS: We demonstrated that the expression of PCA3 is significantly higher in choriocarcinoma cells in contrast to normal human chorionic trophoblast cells. Furthermore, PCA3 could promote cell proliferation, migration and invasion in gestational choriocarcinoma cells and facilitated epithelial to mesenchymal transition (EMT) in vitro. In addition, PAC3 could directly bind to miR-106b and effectively liberate the expression of its endogenous target matrix metallopeptidase 2 (MMP2). CONCLUSION: Our results suggest that PCA3 contributes to the progression of choriocarcinoma by acting as a ceRNA against miR-106b.

3.
Crit Rev Eukaryot Gene Expr ; 28(4): 329-336, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30311581

RESUMO

Ovarian cancer is one of the most malignant gynecological tumors in the world, with a high fatality rate and resistance to chemotherapy. Much basic research has revealed that oxidative stress is involved in tumor occurrence and development processes and is associated with tumor progression as well as metastasis. In recent years, oxidative stress has been proven to have a close connection with malignant biological behavior in ovarian cancer, and this topic has garnered increasing attention. This article reviews the research aimed toward elucidating the relationship between oxidative stress and ovarian cancer.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Fator 2 Relacionado a NF-E2/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Elementos de Resposta Antioxidante , Feminino , Humanos , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Transdução de Sinais
4.
Int J Clin Exp Pathol ; 8(9): 11185-91, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26617840

RESUMO

UNLABELLED: The study was aimed to evaluate the potential biomarkers from pulmonary surfactant protein D (SP-D), Krebs von den Lungen-6 (KL-6), and 56-kD a human type I protein (HTI-56) in serum and bronchoalveolar lavage fluid samples of children with Mycoplasma pneumoniae pneumonia. This retrospective study, self-controlled study enrolled 34 Chinese children with M. pneumoniae pneumonia. The levels of SP-D, KL-6, and HTI-56 in bronchoalveolar lavage fluid samples were assessed and compared between patients with unilateral lung infection and contralateral lungs without any abnormal findings. Significant differences in the levels of SP-D, KL-6, and HTI-56 were observed in infected bronchoalveolar lavage fluid samples compared with uninfected samples (all P<0.05); however, there was no correlation between the serum level of SP-D, KL-6, and HTI-56 and their levels in infected and uninfected bronchoalveolar lavage fluid samples (P>0.05). CONCLUSION: The high levels of SP-D, KL-6, and HTI-56 in infected bronchoalveolar lavage fluid samples may reflect the injury of alveolar epithelium caused by M. pneumoniae. Instead of SP-D in uninfected bronchoalveolar lavage fluid samples obtained by invasive bronchoscopy, serum SP-D may serve as a convenient medium to distinguish lung infection caused by M. pneumoniae.


Assuntos
Líquido da Lavagem Broncoalveolar/química , Proteínas de Membrana/sangue , Mucina-1/sangue , Mycoplasma pneumoniae/patogenicidade , Pneumonia por Mycoplasma/sangue , Proteína D Associada a Surfactante Pulmonar/sangue , Adolescente , Fatores Etários , Biomarcadores/sangue , Broncoscopia , Criança , Pré-Escolar , China , Feminino , Humanos , Lactente , Masculino , Pneumonia por Mycoplasma/diagnóstico , Pneumonia por Mycoplasma/microbiologia , Valor Preditivo dos Testes , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
5.
Tumour Biol ; 2015 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-26383522

RESUMO

Early cancer metastases often occur in cervical cancer (CC) patients, resulting in poor prognosis and poor therapeutic outcome after resection of primary cancer. Hence, there is a compelling requirement for elucidating the molecular mechanisms underlying the CC cell invasiveness. Recently, the role of microRNAs (miRNAs) and pituitary tumor-transforming gene 1 (Pttg1) in the carcinogenesis of CC has been reported. Nevertheless, the relationship between miRNAs and Pttg1 remains ill-defined. Here, we showed that the levels of miR-3666 were significantly decreased and the levels of zinc finger E-box binding homeobox 1 (ZEB1) and Pttg1 were significantly increased in the CC specimens from patients, compared to the paired non-tumor tissue. Moreover, the levels of miR-3666 and ZEB1 inversely correlated. Bioinformatics analyses showed that miR-3666 targeted the 3'-untranslated region (3'-UTR) of ZEB1 messenger RNA (mRNA) to inhibit its translation, which was confirmed by luciferase reporter assay. Moreover, Pttg1 overexpression inhibited miR-3666 and subsequently increased ZEB1 and cell invasion, while Pttg1 depletion increased miR-3666 and subsequently decreased ZEB1 and cell invasion. Together, our data suggest that Pttg1 may increase CC cell metastasis, possibly through miR-3666-regulated ZEB1 levels.

6.
Cardiology ; 132(3): 137-46, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26278917

RESUMO

OBJECTIVE: Macrophage apoptosis plays a key role in atherosclerotic plaque rupture. This study investigated the effects of recombinant human brain natriuretic peptide (BNP) on oxidised low-density lipoprotein (ox-LDL)-induced macrophage apoptosis and explored the underlying mechanism. METHODS: A model of ox-LDL-induced macrophage injury was established to evaluate the role of BNP. Flow cytometry was employed to detect apoptosis and changes in mitochondrial membrane potential (x0394;x03A8;m), and confocal microscopy was used to determine cellular reactive oxygen species (ROS) levels. Additionally, reverse transcription-polymerase chain reaction and colourimetry were used to detect the mRNA expression and activity, respectively, of superoxide dismutase (SOD) and malondialdehyde (MDA). RESULTS: Ox-LDL induced macrophage apoptosis in a concentration-dependent manner, and maximum apoptosis occurred at 100 µg/ml ox-LDL (45.62 ± 2.76 vs. 6.84 ± 1.94%; p < 0.05). Conversely, BNP suppressed macrophage apoptosis, with a maximal effect at 10-9 mol/l (18.56 ± 1.79%; p < 0.05). Compared with the control group, intracellular ROS levels increased, x0394;x03A8;m decreased, SOD mRNA expression and activity decreased and MDA mRNA expression and content increased in the 100-µg/ml ox-LDL group (527.30 ± 36.20 vs. 100.00 ± 0.00%, 3.01 ± 0.52 vs. 9.67 ± 0.51%, 0.53 ± 0.18 vs. 1.00 ± 0.00, 256.6 ± 8.20 vs. 355.8 ± 9.58 U/ml, 1.59 ± 0.23 vs. 1.00 ± 0.00 and 29.4 ± 1.68 vs. 5.94 ± 0.51 nmol/ml; p < 0.05); these effects were significantly counteracted by 10-9 mol/l BNP (237.30 ± 30.62%, 6.55 ± 1.57%, 0.90 ± 0.07, 310.4 ± 2.97 U/ml, 1.14 ± 0.10, 20.54 ± 1.55 nmol/ml; p < 0.05). CONCLUSION: BNP attenuates ox-LDL-induced macrophage apoptosis by suppressing oxidative stress and preventing x0394;x03A8;m loss.


Assuntos
Apoptose/efeitos dos fármacos , Lipoproteínas LDL/farmacologia , Macrófagos/patologia , Peptídeo Natriurético Encefálico/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Técnicas de Cultura de Células , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Humanos , Malondialdeído/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteínas Recombinantes/farmacologia , Superóxido Dismutase/metabolismo
7.
Mol Med Rep ; 12(2): 2622-8, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25954860

RESUMO

Clear-cell renal cell carcinoma (CCRCC) is the most frequent primary malignancy in the adult kidney. Most patients with advanced CCRCC have poor prognosis as CCRCC remains resistant to chemotherapy. The present study explored the possible mechanism underlying CCRCC resistance to chemotherapy and found that loss of PTEN in CCRCC may be involved. Knockdown of PTEN in the CCRCC cell line ACHN blocked etoposide-induced apoptosis and etoposide-impaired cell proliferation was also inhibited. It has been demonstrated that most chemotherapy drugs exert their anti-cancer effects via p53-mediated apoptosis, and in accordance, with this, the present study showed that treatment with etoposide significantly increased p53 levels. Silencing of PTEN in ACHN inhibited the Akt/HDM2 signaling cascade and depressed p53 expression, and the interaction between HDM2 and p53 was also enhanced. This was further verified in CCRCC tissue specimens from patients The results of the present study suggested that loss of PTEN, which deactivated Akt/HDM2 signaling followed by degradation of p53, may contribute to the development of etoposide resistance in CCRCC.


Assuntos
Carcinoma de Células Renais/genética , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Renais/genética , PTEN Fosfo-Hidrolase/genética , Proteínas Proto-Oncogênicas c-akt/genética , Proteína Supressora de Tumor p53/genética , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Etoposídeo/farmacologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Masculino , PTEN Fosfo-Hidrolase/deficiência , Proteólise , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Transdução de Sinais , Proteína Supressora de Tumor p53/metabolismo
8.
Acta Crystallogr Sect E Struct Rep Online ; 70(Pt 10): m341-2, 2014 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-25484671

RESUMO

Two 4,4'-[1,3-phenyl-enebis(-oxy)]dibenzoate anions bridge two 1,10-phenanthroline-chelated Zn(II) cations about a center of inversion to generate the dinuclear title compound, [Zn2(C20H12O6)2(C12H8N2)2]·2H2O. The geometry about the Zn(II) atom is a distorted octa-hedron. In the crystal, the mol-ecules are connected by classical O-H⋯O hydrogen bonds, weak C-H⋯O hydrogen bonds and C-H⋯π inter-actions, forming a three dimensional network. π-π stacking is also observed between aromatic rings of adjacent mol-ecules, centroid-centroid distances are 3.753 (2), 3.5429 (16) and 3.5695 (17) Å.

9.
Acta Crystallogr Sect E Struct Rep Online ; 70(Pt 11): m371, 2014 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-25484780

RESUMO

In the title salt, [Cd(C6H15NO3)2](C8H4O4), the Cd(2+) cation is coordinated by six O atoms and two N atoms from two tetra-dentate 2-[bis-(2-hy-droxy-eth-yl)amino]-ethanol ligands, displaying a distorted square-anti-prismatic coordination. The terephthalate dianion does not coordinate to the cation but is connected through O⋯H-O hydrogen bonds of medium strength to the complex cations, leading to a layered structure extending parallel to (100).

10.
Acta Neuropathol ; 128(5): 679-89, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25107476

RESUMO

Neuronal insulin signaling abnormalities have been associated with Alzheimer's disease (AD). However, the specificity of this association and its underlying mechanisms have been unclear. This study investigated the expression of abnormal serine phosphorylation of insulin receptor substrate 1 (IRS1) in 157 human brain autopsy cases that included AD, tauopathies, α-synucleinopathies, TDP-43 proteinopathies, and normal aging. IRS1-pS(616), IRS1-pS(312) and downstream target Akt-pS(473) measures were most elevated in AD but were also significantly increased in the tauopathies: Pick's disease, corticobasal degeneration and progressive supranuclear palsy. Double immunofluorescence labeling showed frequent co-expression of IRS1-pS(616) with pathologic tau in neurons and dystrophic neurites. To further investigate an association between tau and abnormal serine phosphorylation of IRS1, we examined the presence of abnormal IRS1-pS(616) expression in pathological tau-expressing transgenic mice and demonstrated that abnormal IRS1-pS(616) frequently co-localizes in tangle-bearing neurons. Conversely, we observed increased levels of hyperphosphorylated tau in the high-fat diet-fed mouse, a model of insulin resistance. These results provide confirmation and specificity that abnormal phosphorylation of IRS1 is a pathological feature of AD and other tauopathies, and provide support for an association between insulin resistance and abnormal tau as well as amyloid-ß.


Assuntos
Doença de Alzheimer/patologia , Encéfalo/metabolismo , Proteínas Substratos do Receptor de Insulina/metabolismo , Serina/metabolismo , Tauopatias/patologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Animais , Proteínas de Ligação a DNA/metabolismo , Dieta Hiperlipídica/efeitos adversos , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Pessoa de Meia-Idade , Fosforilação/genética , Proteinopatias TDP-43/patologia , alfa-Sinucleína/metabolismo , Proteínas tau/genética , Proteínas tau/metabolismo
11.
Zhonghua Yi Xue Za Zhi ; 93(7): 500-3, 2013 Feb 19.
Artigo em Chinês | MEDLINE | ID: mdl-23660316

RESUMO

OBJECTIVE: To explore the alteration of collagen ultrastructure and content in uterine ligaments and paraurethral tissue and explore whether the alteration may contribute to stress urinary incontinence (SUI) and pelvic organ prolapse (POP). METHODS: The cardinal ligament, uterosacral ligament and paraurethral tissue samples were obtained from 90 subjects undergoing hysterectomy. Collagen ultrastructure was examined with transmission electron microscopy. And collagen content and expression of vasoactive intestinal peptide (VIP) were examined with immunohistochemistry. RESULTS: The smooth muscle fascicles were thinner in the patients of SUI and POP. Arrangement of smooth muscle fascicles was disorderly. Fibroblast was metabolically active. The mean collagen fibril diameters in the SUI and POP groups were larger than that in the control group (P < 0.01). The mean contents of collagen I and III in the SUI and POP groups were lower than that in the control group (P < 0.01). The expression of VIP was lower (P < 0.05). CONCLUSION: Predominance of collagen degradation during tissue repair may contribute to and promote POP and SUI. The decrease of VIP might be related with nerve damage or degeneration to cause or accelerate the progress of pelvic organ prolapse.


Assuntos
Colágeno/ultraestrutura , Prolapso de Órgão Pélvico/patologia , Incontinência Urinária por Estresse/patologia , Peptídeo Intestinal Vasoativo/metabolismo , Colágeno/metabolismo , Feminino , Humanos , Pessoa de Meia-Idade , Diafragma da Pelve/patologia , Prolapso de Órgão Pélvico/metabolismo , Incontinência Urinária por Estresse/metabolismo
12.
Asian Pac J Cancer Prev ; 14(3): 2113-8, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23679328

RESUMO

AIM AND BACKGROUND: Cervical cancer remains the third most common cancer in women globally after breast and colorectal cancer. Well-characterized biomarkers are necessary for early diagnosis and to predict metastatic progression and effective therapy. MiRNAs can regulate gene expression, cell growth, differentiation and apoptosis by targeting mRNAs for translational repression or degradation in tumor cells. The present study was conducted to assess expression of miR93, miR200a, RECK, MMP2, MMP9 in invasive cervical carcinoma, and analyze their clinical significance. METHOD: A total of 116 patients with invasive cervical carcinoma and 100 patients undergoing hysterectomy for benign lesions were retrospectively examined. Quantitative real-time PCR was performed to determine expression of miR93 and miR200a while RECK, MMP2, MMP9 and MVD were assessed by immunohistochemical staining. RESULTS: Cervical carcinoma patients demonstrated up-regulation of miR-93, miR-200a, MMP2 and MMP9, with down-regulation of RECK as compared to benign lesion tissues. RECK was significantly inversely related to invasion and lymphatic metastasis. The 5-year survival rate for patients with strong RECK expression was significantly higher than that with weakly expressing tumors. CONCLUSION: MiR-93 and miR-200a are associated with metastasis and invasion of cervical carcinoma. Thus together with RECK they are potential prognostic markers for cervical carcinoma. RECK cooperating with MMP2, MMP9 expression is a significant prognostic factor correlated with long-term survival for patients with invasive cervical carcinoma.


Assuntos
Proteínas Ligadas por GPI/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , MicroRNAs/genética , Neoplasias do Colo do Útero/mortalidade , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidade , Adenocarcinoma/cirurgia , Adulto , Idoso , Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/cirurgia , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Metástase Linfática , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real , Taxa de Sobrevida , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/cirurgia
13.
Neurobiol Aging ; 34(1): 157-68, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22554416

RESUMO

Although neuritic plaques and neurofibrillary tangles in older adults are correlated with cognitive impairment and severity of dementia, it has long been recognized that the relationship is imperfect, as some people exhibit normal cognition despite high levels of Alzheimer's disease (AD) pathology. We compared the cellular, synaptic, and biochemical composition of midfrontal cortices in female subjects from the Religious Orders Study who were stratified into three subgroups: (1) pathological AD with normal cognition ("AD-Resilient"), (2) pathological AD with AD-typical dementia ("AD-Dementia"), and (3) pathologically normal with normal cognition ("Normal Comparison"). The AD-Resilient group exhibited preserved densities of synaptophysin-labeled presynaptic terminals and synaptopodin-labeled dendritic spines compared with the AD-Dementia group, and increased densities of glial fibrillary acidic protein astrocytes compared with both the AD-Dementia and Normal Comparison groups. Further, in a discovery-type antibody microarray protein analysis, we identified a number of candidate protein abnormalities that were associated with a particular diagnostic group. These data characterize cellular and synaptic features and identify novel biochemical targets that may be associated with resilient cognitive brain aging in the setting of pathological AD.


Assuntos
Doença de Alzheimer/complicações , Encéfalo/patologia , Transtornos Cognitivos , Proteínas do Tecido Nervoso/metabolismo , Neurônios/patologia , Sinapses/patologia , Idoso , Idoso de 80 Anos ou mais , Encéfalo/metabolismo , Encéfalo/ultraestrutura , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/metabolismo , Transtornos Cognitivos/patologia , Feminino , Proteína Glial Fibrilar Ácida/metabolismo , Humanos , Masculino , Microscopia Eletrônica de Transmissão , Neurônios/ultraestrutura , Fosfopiruvato Hidratase , Análise Serial de Proteínas , Sinapses/ultraestrutura , Proteínas tau/metabolismo
14.
Chin Med J (Engl) ; 125(18): 3246-50, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22964317

RESUMO

BACKGROUND: Myelosuppression is the main dose-related toxicity of many chemotherapeutic drugs. The human multidrug resistance (mdr1) gene is well-known for its ability to confering drug resistance. In this study, we meant to transplant the placenta mesenchymal stem cells (P-MSCs) moderated by mdr1 gene into a nude mice model radiated by γ-Co(60) and to explore the chemoprotection for bone marrow (BM) toxicity. METHODS: Human P-MSCs were isolated from trypsin-digested term placentas and then transduced by with reconstructed retroviral vector containing mdr1 gene and green fluorescent protein (GFP) reporter gene. The integration and expression of mdr1 gene was observed indirectedly by the expression of GFP. A nude mice model was constructed after irradiation with a sublethal dosage of γ-Co(60). These irradiated mice were transplanted with mdr1-MSCs through the caudal vein and then received paclitaxel (PAC) intraperitoneal chemotherapy. The Peripheral peripheral blood (PB) of the nude mice was collected, and the PB cells counts and values were determined using an automatic analyzer. RESULTS: After PAC treatment, mdr1-MSCs transplanted mice showed markedly improved survival upon compared to MSCs transplanted mice (85.7% vs. 57.1%). White blood cell (WBC) and red blood cell (RBC) counts as well as the hemoglobin (Hb) values were significantly increased in PAC treated mdr1-MSCs mice compared to PAC treated control mice when PAC chemotherapy had been finished (all P < 0.05), but the difference was not found in the plateltes (PLT) count (P > 0.05). CONCLUSION: Human P-MSCs moderated by mdr1 gene when transplanted into nude mice may provide chemoprotection for hematopoietic toxicity.


Assuntos
Genes MDR/fisiologia , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Animais , Medula Óssea , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Células Cultivadas , Eritrócitos/metabolismo , Feminino , Genes MDR/genética , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Hemoglobinas/metabolismo , Humanos , Leucócitos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Placenta/citologia , Gravidez
15.
J Clin Invest ; 122(4): 1316-38, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22476197

RESUMO

While a potential causal factor in Alzheimer's disease (AD), brain insulin resistance has not been demonstrated directly in that disorder. We provide such a demonstration here by showing that the hippocampal formation (HF) and, to a lesser degree, the cerebellar cortex in AD cases without diabetes exhibit markedly reduced responses to insulin signaling in the IR→IRS-1→PI3K signaling pathway with greatly reduced responses to IGF-1 in the IGF-1R→IRS-2→PI3K signaling pathway. Reduced insulin responses were maximal at the level of IRS-1 and were consistently associated with basal elevations in IRS-1 phosphorylated at serine 616 (IRS-1 pS6¹6) and IRS-1 pS6³6/6³9. In the HF, these candidate biomarkers of brain insulin resistance increased commonly and progressively from normal cases to mild cognitively impaired cases to AD cases regardless of diabetes or APOE ε4 status. Levels of IRS-1 pS6¹6 and IRS-1 pS6³6/6³9 and their activated kinases correlated positively with those of oligomeric Aß plaques and were negatively associated with episodic and working memory, even after adjusting for Aß plaques, neurofibrillary tangles, and APOE ε4. Brain insulin resistance thus appears to be an early and common feature of AD, a phenomenon accompanied by IGF-1 resistance and closely associated with IRS-1 dysfunction potentially triggered by Aß oligomers and yet promoting cognitive decline independent of classic AD pathology.


Assuntos
Doença de Alzheimer/metabolismo , Encéfalo/metabolismo , Transtornos Cognitivos/etiologia , Proteínas Substratos do Receptor de Insulina/fisiologia , Resistência à Insulina , Fator de Crescimento Insulin-Like I/farmacologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/patologia , Doença de Alzheimer/psicologia , Apolipoproteína E4/genética , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Córtex Cerebelar/metabolismo , Córtex Cerebelar/patologia , Transtornos Cognitivos/metabolismo , Complicações do Diabetes/complicações , Resistência a Medicamentos , Feminino , Glucose/metabolismo , Hipocampo/metabolismo , Hipocampo/patologia , Humanos , Insulina/metabolismo , Insulina/farmacologia , Proteínas Substratos do Receptor de Insulina/química , Proteínas Substratos do Receptor de Insulina/genética , Fator de Crescimento Insulin-Like I/fisiologia , Masculino , Pessoa de Meia-Idade , Fosforilação , Fosfosserina/metabolismo , Processamento de Proteína Pós-Traducional , Proteínas Recombinantes/farmacologia , Transdução de Sinais
16.
Zhonghua Yi Xue Za Zhi ; 92(41): 2930-3, 2012 Nov 06.
Artigo em Chinês | MEDLINE | ID: mdl-23328244

RESUMO

OBJECTIVE: To explore the feasibility and safety of mdr1 gene transferred into placenta derived mesenchymal stem cells (P-MSCs) by reconstructed retroviral vector. METHODS: Human P-MSCs were isolated and expanded by Percoll density gradient and then transduced repeatedly by reconstructed retroviral vector containing mdr1 gene. The transfection and expression of mdr1 gene was detected by reverse transcription-polymerase chain reaction (RT-PCR) and fluorescence-activated cell sorting (FACS). Meanwhile, the biological features of mdr1-MSCs were identified and analyzed. RESULTS: The expression of mdr1mRNA was found in transfected cells. The expression of P-glycoprotein (P-gp) encoded by mdr1 gene was (27.6 ± 5.1)% in the transfected P-MSCs cells versus (0.4 ± 0.1)% in the non-transfected P-MSCs cells (t = 14.291, P < 0.01). The percent of P-MSCs at quiescent phase (G0/G1 phase) was around 95.40% and it was in accord with the characterization of stem cells. The mdr1-MSCs exhibited typical ultrastructures of low-differentiated stem cells. Moreover, they still retained the potency of adipogenic and osteogenic differentiation in the presence of appropriate conditioned media. CONCLUSION: A stable expression of P-gp may be obtained by reconstructed retroviral-mediated transfection in vitro. And transfected MSCs retain the characteristics of stem cells.


Assuntos
Resistência a Múltiplos Medicamentos/genética , Genes MDR , Células-Tronco Mesenquimais/citologia , Placenta/citologia , Transfecção , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Células Cultivadas , Feminino , Vetores Genéticos , Humanos , Gravidez
17.
Acta Crystallogr Sect E Struct Rep Online ; 67(Pt 4): m397, 2011 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-21753933

RESUMO

In the title compound, {[Zn(C(8)H(5)N(2)O(2)S)(2)]·3H(2)O}(n), the Zn(II) atom, lying on a twofold rotation axis, is four-coordinated by two S atoms and two O atoms from four 2-sulfido-1H-benzimidazol-3-ium-5-carboxyl-ate (H(2)mbidc) ligands in a distorted tetra-hedral geometry. Two H(2)mbidc ligands bridge two Zn(II) atoms, generating a double-chain along [[Formula: see text]01]. Adjacent chains are linked by N-H⋯O and O-H⋯O hydrogen bonds, forming a three-dimensional supra-molecular network. One of the two water molecules also lies on a twofold rotation axis.

19.
Synapse ; 65(8): 763-70, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21190219

RESUMO

Animal models provide compelling evidence that chronic stress is associated with biochemical and morphological changes in the brain, many of which are mediated by corticosterone, a principal glucocorticoid synthesized in the rodent adrenal cortex and secreted in response to stress. To better characterize the effects of chronic corticosterone at the synaptic and subsynaptic level, we implanted three-month-old male C57B/6 mice with 2 × 5 mg corticosterone pellets (CORT group, n = 14), 21 day release formulation (20 mg/kg/day dose) or placebo pellets (Placebo group, n = 14), 21-day release formulation. After 20 days, brains were removed. One hemisphere was frozen for biochemical analysis by synaptosomal fractionation with Western blotting, and the other hemisphere was fixed for immunohistochemistry. Localization and expression levels for PSD-95, NR1, and synaptopodin proteins were assessed. Biochemical analysis revealed lower protein levels of PSD-95 (32% decrease, P < 0.001), NR1 (47%, P = 0.01), and synaptopodin (65%, P < 0.001) in the postsynaptic density subsynaptic fraction of the CORT group. Optical densitometry in immunohistochemically labeled sections also found lower levels of PSD-95 in synaptic fields of the dentate gyrus (PSD-95, 33% decrease, P < 0.001; NR1, 31%, P < 0.001; synaptopodin, 40%, P < 0.001) and the CA3 stratum lucidum (36%, P < 0.001, 40%, P < 0.001, and 35%, P < 0.001) of the CORT group. While mechanistic relationships for these changes are not yet known, we speculate that synaptopodin, which is involved in regulation of spine calcium kinetics and posttranslational modification and transport of locally synthesized proteins, may play an important role in the changes of PSD-95 and NR1 protein levels and other synaptic alterations.


Assuntos
Encéfalo/metabolismo , Corticosterona/metabolismo , Guanilato Quinases/metabolismo , Proteínas de Membrana/metabolismo , Proteínas dos Microfilamentos/metabolismo , Densidade Pós-Sináptica/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Animais , Western Blotting , Proteína 4 Homóloga a Disks-Large , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Densidade Pós-Sináptica/química
20.
Ann Neurol ; 67(4): 462-9, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20437581

RESUMO

OBJECTIVE: Olfactory dysfunction is common in Alzheimer disease (AD) and other neurodegenerative diseases. Paired helical filament (PHF)-tau, alpha-synuclein, and amyloid-beta lesions occur early and severely in cerebral regions of the olfactory system, and they have also been observed in olfactory epithelium (OE). However, their frequency, abundance, and disease specificity, and the relationships of OE pathology to brain pathology have not been established. METHODS: We investigated the pathological expression of amyloid-beta, PHFtau, alpha-synuclein, and TDP-43 in postmortem OE of 79 cases with AD, 63 cases with various other neurodegenerative diseases, and 45 neuropathologically normal cases. RESULTS: Amyloid-beta was present as punctate and small patchy aggregates in 71% of AD cases, compared with 22% of normal cases and 14% of cases with other diseases, and in greater amounts in AD than in either of the other 2 diagnostic categories. PHFtau was evident in dystrophic neurites in 55% of cases with AD, 34% with normal brains, and 39% with other neurodegenerative diseases, also at higher densities in AD. alpha-Synuclein was present in dystrophic neurites in 7 cases, 6 of which also had cerebral Lewy bodies. Pathological TDP-43 inclusions were not observed in the OE in any cases. Amyloid-beta and to a lesser degree, PHFtau ratings in OE significantly correlated with cortical Abeta and PHFtau lesion ratings in the brain. INTERPRETATION: These data demonstrate that AD pathology in the OE is present in the majority of cases with pathologically verified AD and correlates with brain pathology. Future work may assess the utility of amyloid-beta and PHFtau measurement in OE as a biomarker for AD.


Assuntos
Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Emaranhados Neurofibrilares/metabolismo , Mucosa Olfatória/metabolismo , Mucosa Olfatória/patologia , Proteínas tau/metabolismo , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Proteínas de Ligação a DNA/metabolismo , Feminino , Humanos , Corpos de Lewy/metabolismo , Corpos de Lewy/patologia , Masculino , Emaranhados Neurofibrilares/patologia , Estatística como Assunto , alfa-Sinucleína/metabolismo
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