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1.
J Nat Prod ; 86(10): 2379-2390, 2023 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-37796721

RESUMO

Euphorbia diterpenoids possess inhibitory effects of Kv1.3 ion channel, but most of this research has focused on diterpenoids with jatrophane-related or ingenane-related skeletons. In the present study, nine undescribed (1-9) and 16 known (10-25) diterpenoids, based on jatrophane, lathyrane, ingenane, abietane, and atisane skeletons, were identified from the methanol extract of the aerial parts of Euphorbia fischeriana. The structures were established by analysis of the spectroscopic data as well as by single-crystal X-ray diffraction analysis. Among the isolated diterpenoids, macrocyclic jatrophanes and lathyranes exerted Kv1.3 blocking activity. Compound 8 exhibited good selectivity on the inhibition of the Kv 1.3 channel rather than hERG channel, with a selectivity index over 7.0. The selective activity of lathyrane diterpenoids indicates that macrocyclic diterpenoids have the potential to be further investigated as therapeutic agents for the treatment of autoimmune diseases.


Assuntos
Diterpenos , Euphorbia , Estrutura Molecular , Euphorbia/química , Diterpenos/farmacologia , Diterpenos/química
2.
Molecules ; 28(13)2023 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-37446560

RESUMO

In this study, we investigated the protective effect of Astragaloside IV (Ast) on mouse podocytes and its possible mechanism of action by constructing a cadmium-induced mouse renal podocytes model. We investigated the effects of cadmium (Cd) toxicity on cell number, morphology, the mitochondrial status of subcellular organelles, protein and gene levels, and the protective effects of Ast by constructing a model of Cd-induced damage to mouse renal podocytes (MPC5) and giving Ast protection at the same time. The results showed that exposure of MPC5 cells to CdCl2 culture medium containing 6.25 µM concentration acted with low cell mortality, but the mortality of MPC5 cells increased with the prolongation of cadmium exposure time. Given Ast, the death rate in the low dose group (12.5 µM) was significantly reduced, while the death rate in the medium dose group (25 µM) was extremely significantly reduced. In comparison to the control group, the Cd-exposed group exhibited a significant increase of 166.7% in malondialdehyde (MDA) content and a significant decrease of 17.1% in SOD activity. The mitochondrial membrane potential was also reduced to varying degrees. However, in the Ast-protected group compared to the Cd-exposed group, the MDA content significantly decreased by 20.8%, the SOD activity decreased by 7.14%, and the mitochondrial membrane potential showed a significant increase. Fluorescence staining of mitochondrial membrane potential indicated that Cd exposure caused mitochondrial apoptosis. In the 12-h cadmium-exposed group, the protein expression of Nephrin in mice significantly decreased by 33.4%. However, the expression of the Desmin protein significantly increased by 67.8%, and the expression of the autophagy protein LC3-II significantly increased by 55.5%. Meanwhile, the expression of PINK1, a mitochondrial autophagy pathway protein, was significantly increased in the 12 h and 24 h cadmium exposure groups. The mRNA level of PINK1 was significantly increased, and that of Parkin was decreased in the 48 h cadmium exposure group. Compared to the Cd-exposed group, the Ast group showed more significant improvements in the expression of podocyte structure, functional proteins, and mitochondrial autophagy pathway proteins. The immunological assay of mitochondrial autophagic pathway proteins further indicated that Cd-induced damage to MPC5 cells might be associated with the dysregulation of mitochondrial autophagy.


Assuntos
Cádmio , Podócitos , Camundongos , Animais , Cádmio/metabolismo , Podócitos/metabolismo , Apoptose , Superóxido Dismutase/metabolismo , Proteínas Quinases/metabolismo
3.
Epilepsia ; 63(8): 1899-1919, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35706131

RESUMO

Ongoing challenges in diagnosing focal cortical dysplasia (FCD) mandate continuous research and consensus agreement to improve disease definition and classification. An International League Against Epilepsy (ILAE) Task Force (TF) reviewed the FCD classification of 2011 to identify existing gaps and provide a timely update. The following methodology was applied to achieve this goal: a survey of published literature indexed with ((Focal Cortical Dysplasia) AND (epilepsy)) between 01/01/2012 and 06/30/2021 (n = 1349) in PubMed identified the knowledge gained since 2012 and new developments in the field. An online survey consulted the ILAE community about the current use of the FCD classification scheme with 367 people answering. The TF performed an iterative clinico-pathological and genetic agreement study to objectively measure the diagnostic gap in blood/brain samples from 22 patients suspicious for FCD and submitted to epilepsy surgery. The literature confirmed new molecular-genetic characterizations involving the mechanistic Target Of Rapamycin (mTOR) pathway in FCD type II (FCDII), and SLC35A2 in mild malformations of cortical development (mMCDs) with oligodendroglial hyperplasia (MOGHE). The electro-clinical-imaging phenotypes and surgical outcomes were better defined and validated for FCDII. Little new information was acquired on clinical, histopathological, or genetic characteristics of FCD type I (FCDI) and FCD type III (FCDIII). The survey identified mMCDs, FCDI, and genetic characterization as fields for improvement in an updated classification. Our iterative clinico-pathological and genetic agreement study confirmed the importance of immunohistochemical staining, neuroimaging, and genetic tests to improve the diagnostic yield. The TF proposes to include mMCDs, MOGHE, and "no definite FCD on histopathology" as new categories in the updated FCD classification. The histopathological classification can be further augmented by advanced neuroimaging and genetic studies to comprehensively diagnose FCD subtypes; these different levels should then be integrated into a multi-layered diagnostic scheme. This update may help to foster multidisciplinary efforts toward a better understanding of FCD and the development of novel targeted treatment options.


Assuntos
Epilepsia , Malformações do Desenvolvimento Cortical do Grupo I , Malformações do Desenvolvimento Cortical , Consenso , Epilepsia/diagnóstico , Epilepsia/patologia , Humanos , Imageamento por Ressonância Magnética , Malformações do Desenvolvimento Cortical/diagnóstico por imagem , Malformações do Desenvolvimento Cortical/genética , Malformações do Desenvolvimento Cortical do Grupo I/diagnóstico , Neuroimagem , Estudos Retrospectivos
4.
Int J Med Sci ; 18(9): 2017-2022, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33850472

RESUMO

Blood blister-like aneurysms (BBAs) are rare and usually appear at nonbranching sites in the supraclinoid portion of the internal carotid artery (ICA). Because it is difficult to obtain histological specimens of the aneurysm wall and because experimental models are challenging to establish, the pathogenesis of BBAs remains uncertain. In this paper, we reviewed the diagnostic, radiological, and pathophysiological characteristics of patients with BBAs. We also summarized the existing evidence and potential mechanisms related to the causes of BBAs. Current evidence indicates that atherosclerosis and dissection are the main prerequisites for the formation of BBAs. Hemodynamics may play a role in the process of BBA formation due to the unique vascular anatomy of the supraclinoid ICA. Further research on histopathology and hemodynamics is warranted in this field.


Assuntos
Aneurisma Roto/etiologia , Doenças das Artérias Carótidas/etiologia , Artéria Carótida Interna/patologia , Aneurisma Intracraniano/etiologia , Aneurisma Roto/diagnóstico , Aneurisma Roto/patologia , Aneurisma Roto/terapia , Doenças das Artérias Carótidas/diagnóstico , Doenças das Artérias Carótidas/patologia , Doenças das Artérias Carótidas/terapia , Artéria Carótida Interna/diagnóstico por imagem , Artéria Carótida Interna/cirurgia , Angiografia Cerebral , Embolização Terapêutica , Procedimentos Endovasculares/instrumentação , Procedimentos Endovasculares/métodos , Humanos , Aneurisma Intracraniano/diagnóstico , Aneurisma Intracraniano/patologia , Aneurisma Intracraniano/terapia , Microcirurgia/métodos , Stents , Resultado do Tratamento
5.
Phytother Res ; 35(2): 954-973, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32893437

RESUMO

Blood-brain barrier (BBB) dysfunction has been implicated in Alzheimer's disease (AD) and is closely linked to the release of proinflammatory cytokines in brain capillary endothelial cells. We have previously reported that lychee seed polyphenols (LSP) exerted anti-neuroinflammatory effect. In this study, we aimed to explore the protective effect of LSP on BBB integrity. The monolayer permeability of bEnd.3 cells, and the mRNA level and protein expression of tight junction proteins (TJs), including Claudin 5, Occludin, and ZO-1, were examined. In addition, the inhibition of Aß(25-35)-induced NLRP3 inflammasome activation, and the autophagy induced by LSP were investigated by detecting the expression of NLRP3, caspase-1, ASC, LC3, AMPK, mTOR, and ULK1. Furthermore, the cognitive function and the expression of TJs, NLRP3, caspase-1, IL-1ß, and p62 were determined in APP/PS1 mice. The results showed that LSP significantly decreased the monolayer permeability and inhibited the NLRP3 inflammasome in Aß(25-35)-induced bEnd3 cells. In addition, LSP induced autophagy via the AMPK/mTOR/ULK1 pathway in bEnd.3 cells, and improved the spatial learning and memory function, increased the TJs expression, and inhibited the expression of NLRP3, caspase-1, IL-1ß, and p62 in APP/PS1 mice. Therefore, LSP protects BBB integrity in AD through inhibiting Aß(25-35)-induced NLRP3 inflammasome activation via the AMPK/mTOR/ULK1-mediated autophagy.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Doença de Alzheimer/tratamento farmacológico , Autofagia/efeitos dos fármacos , Barreira Hematoencefálica/efeitos dos fármacos , Inflamassomos/efeitos dos fármacos , Litchi/química , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Polifenóis/uso terapêutico , Sementes/química , Animais , Masculino , Camundongos , Camundongos Transgênicos , Polifenóis/farmacologia , Transfecção
6.
Bioorg Med Chem Lett ; 30(6): 126966, 2020 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-32001136

RESUMO

Herein, we report the discovery of a series of thieno[2,3-d]pyrimidin-4(3H)-one derivatives as a new class of ROCK inhibitors. Structure-activity relationship studies of these compounds led to the identification of the most potent compound, 3-(3-methoxybenzyl)-6-(1H-pyrrolo[2,3-b]pyridin-4-yl)thieno[2,3-d]pyrimidin-4(3H)-one (8k), which showed IC50 values of 0.004 µM and 0.001 µM against ROCK Ⅰ and ROCK Ⅱ, respectively. In vitro, 8k significantly reduced the phosphorylation level of ROCK downstream signaling protein and induce changes in cell morphology and migration. Overall, this study provides a promising lead compound for drug discovery targeting ROCKs.


Assuntos
Inibidores de Proteínas Quinases/química , Pirimidinonas/química , Quinases Associadas a rho/antagonistas & inibidores , Movimento Celular/efeitos dos fármacos , Descoberta de Drogas , Humanos , Fosforilação , Inibidores de Proteínas Quinases/metabolismo , Pirimidinonas/metabolismo , Relação Estrutura-Atividade
7.
Clin Neuropathol ; 39(6): 263-270, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32589128

RESUMO

AIMS: To evaluate the occurrence and diagnostic value of MYB-QKI rearrangement status in angiocentric glioma (AG) in Chinese patients. MATERIALS AND METHODS: 27 cases were collected from six hospitals, followed by a retrospective analysis of clinical, radiological, and morphological data. MYB protein expression was assessed by immunohistochemical staining (IHC), and the MYB-QKI rearrangement was detected by fluorescence in situ hybridization (FISH). RESULTS: Among the 27 cases (16 males), the median age at surgery was 17 years (range 3 - 43 years); 24 (88.9%) cases had a history of refractory epilepsy, and the mean history of pre-surgical epilepsy was 13 years (range 1.5 - 27 years); 26 (96.3%) cases had lesions located in the superficial cerebrocortical regions, and 1 (3.7%) case had a lesion in the brainstem. Except for the classic histological features, the involvement of superficial cortex extending to the leptomeninges, microcalcification, and cystic pattern with microcystic formations was observed in 11 (40.7%), 3 (11.1%), and 4 (14.8%) cases, respectively. IHC showed that all 27 cases were positive for glial fibrillary acidic protein (GFAP) and vimentin, and negative for neuronal nuclear antigen (NeuN). The positive rates of epithelial membrane antigen (EMA) and D2-40 were 81.5% (22/27) and 74.1% (20/27), respectively. A total of 14 (51.9%) cases were positive for MYB. The rate of Ki-67 proliferation was 1 - 5% in 25 cases, and in 2 cases with anaplastic features it was 10 and 20%. MYB-QKI rearrangement was revealed by FISH examination in 95.8% (23/24) of the AGs, including 3 cases with atypical histological appearance. CONCLUSION: Compared to IHC, FISH was more appropriate for detecting MYB-QKI rearrangement. MYB-QKI rearrangement was detected in the majority of Chinese AG cases, and therefore represents a potential diagnostic biomarker for AG.


Assuntos
Biomarcadores Tumorais/análise , Glioma/metabolismo , Glioma/patologia , Proteínas Proto-Oncogênicas c-myb/metabolismo , Proteínas de Ligação a RNA/metabolismo , Adolescente , Adulto , Carcinoma Adenoide Cístico/metabolismo , Carcinoma Adenoide Cístico/patologia , Criança , Pré-Escolar , Epilepsia/diagnóstico , Epilepsia/metabolismo , Epilepsia/patologia , Feminino , Proteína Glial Fibrilar Ácida/metabolismo , Humanos , Masculino , Proteínas de Ligação a RNA/genética , Estudos Retrospectivos , Adulto Jovem
8.
Neuropathology ; 40(6): 627-631, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32954563

RESUMO

Cartilaginous metaplasia is rare in primary central nervous system (CNS) neoplasms and has not been described in the histone 3 (H3) gene (H3) with a substitution of lysine to methionine (H3 K27M mutant) diffuse midline glioma before. Here, we report a case of H3 K27M mutant diffuse midline glioma with cartilaginous metaplasia in a 56-year-old woman. Magnetic resonance imaging (MRI) revealed a ring-enhanced lesion located in the medulla oblongata and extended superiorly into the fourth ventricle. The tumor was macroscopically completely resected. Histologically, the tumor was composed of a gliomatous component and a well-differentiated cartilaginous component. Microvascular proliferation and necrosis were noted. According to immunohistochemical staining, glial cells were diffusely and strongly positive for glial fibrillary acidic protein (GFAP), oligodendrocyte lineage transcription factor 2 (Olig2), H3 K27M, and S-100 protein but negative for H3K27me3. The chondrocytes also were positive for GFAP and S-100 protein. The H3 K27M mutation was confirmed by sequencing in both the gliomatous and cartilaginous components, suggesting a common origin from the same progenitor cells. Based on these findings, the tumor was diagnosed as a diffuse midline glioma with H3 K27M mutation with widespread cartilaginous metaplasia, corresponding to WHO grade IV. This is an extremely rare H3 K27M mutant diffuse midline glioma with cartilaginous metaplasia, and reporting this unusual case adds to the understanding of this tumor type.


Assuntos
Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Cartilagem/patologia , Glioma/genética , Glioma/patologia , Histonas/genética , Feminino , Humanos , Metaplasia/patologia , Pessoa de Meia-Idade , Mutação
9.
Epilepsia ; 59(9): 1796-1806, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30079598

RESUMO

OBJECTIVE: Microglial abnormalities have been reported in pathologic specimens from patients with tuberous sclerosis complex (TSC), a genetic disorder characterized by epilepsy, intellectual disability, and autism. However, the pathogenic role of microglia in epilepsy in TSC is poorly understood, particularly whether microglia defects may be a primary contributor to epileptogenesis or are secondary to seizures or simply epiphenomena. In this study, we tested the hypothesis that Tsc1 gene inactivation in microglia is sufficient to cause epilepsy in mouse models of TSC. METHODS: Using a chemokine receptor, Cx3cr1, to target microglia, conventional Tsc1Cx3cr1-Cre CKO (conditional knockout) mice and postnatal-inducible Tsc1Cx3cr1-CreER CKO mice were generated and assessed for molecular and histopathologic evidence of microglial abnormalities, mechanistic target of rapamycin 1 (mTORC1) pathway activation, and epilepsy. RESULTS: Tsc1Cx3cr1-Cre CKO mice exhibited a high efficiency of microglia Tsc1 inactivation, mTORC1 activation, increased microglial size and number, and robust epilepsy, which were rapamycin-dependent. However, Cre reporter studies demonstrated that constitutive Cx3cr1 expression affected not only microglia, but also a large percentage of cortical neurons, confounding the role of microglia in epileptogenesis in Tsc1 Cx3cr1-Cre CKO mice. In contrast, postnatal inactivation of Tsc1 utilizing a tamoxifen-inducible Cx3cr1-CreER resulted in a more-selective microglia Tsc1 inactivation with high efficiency, mTORC1 activation, and increased microglial size and number, but no documented epilepsy. SIGNIFICANCE: Microglia abnormalities may contribute to epileptogenesis in the context of neuronal involvement in TSC mouse models, but selective Tsc1 gene inactivation in microglia alone may not be sufficient to cause epilepsy, suggesting that microglia have more supportive roles in the pathogenesis of seizures in TSC.


Assuntos
Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Microglia/patologia , Esclerose Tuberosa/patologia , Esclerose Tuberosa/fisiopatologia , Animais , Animais Recém-Nascidos , Encéfalo/patologia , Receptor 1 de Quimiocina CX3C/genética , Receptor 1 de Quimiocina CX3C/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Modelos Animais de Doenças , Eletroencefalografia , Antagonistas de Estrogênios/farmacologia , Regulação da Expressão Gênica/genética , Proteína Glial Fibrilar Ácida/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas dos Microfilamentos/metabolismo , Microglia/efeitos dos fármacos , Microglia/metabolismo , Fosfopiruvato Hidratase/metabolismo , Sirolimo/farmacologia , Estatísticas não Paramétricas , Tamoxifeno/farmacologia , Esclerose Tuberosa/tratamento farmacológico , Esclerose Tuberosa/genética , Proteína 1 do Complexo Esclerose Tuberosa/genética , Proteína 1 do Complexo Esclerose Tuberosa/metabolismo , Gravação em Vídeo
10.
Epilepsia ; 58(10): 1697-1705, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28833053

RESUMO

OBJECTIVE: In 2011, the International League Against Epilepsy (ILAE) proposed a consensus classification system of focal cortical dysplasia (FCD) to distinguish clinicopathological subtypes, for example, "isolated" FCD type Ia-c and IIa-b, versus "associated" FCD type IIIa-d. The histopathological differentiation of FCD type I and III variants remains, however, a challenging issue in everyday practice. We present a unique histopathological pattern in patients with difficult-to-diagnose FCD, which highlights this dilemma, but also helps to refine the current ILAE classification scheme of FCD. METHODS: We present a retrospective series of 11 male and one female patient with early onset pharmacoresistant epilepsy of the posterior quadrant (mean age at seizure onset = 4.6 years). All surgical specimens were reviewed. Clinical histories were retrieved and extracted from archival patient files. RESULTS: Microscopic inspection revealed abnormalities in cortical architecture with complete loss of layer 4 in all surgical samples of the occipital lobe, as confirmed by semiquantitative measurements (p < 0.01). Clinical history reported early transient hypoxic condition in nine patients (75%). Magnetic resonance imaging (MRI) revealed abnormal signals in the occipital lobe in all patients, and signal changes suggestive of subcortical encephalomalacia were found in seven patients. Surgical treatment achieved favorable seizure control (Engel class I and II) in seven patients with an available follow-up period of 6.1 years. SIGNIFICANCE: Prominent disorganization of cortical layering and lack of any other microscopically visible principle lesion in the surgical specimen would result in this neuropathological pattern hitherto being classified as FCD ILAE type Ib. However, perinatal hypoxia with distinctive MRI changes suggested primarily a hypoxemic lesion and acquired pathomechanism of neuronal cell loss in the occipital lobe of our patient series. We propose, therefore, classifying this distinctive clinicopathological pattern as a separate variant of FCD ILAE type IIId.


Assuntos
Epilepsia/patologia , Malformações do Desenvolvimento Cortical/patologia , Lobo Occipital/patologia , Adolescente , Criança , Epilepsia/classificação , Epilepsia/diagnóstico por imagem , Epilepsia/cirurgia , Feminino , Humanos , Hipóxia-Isquemia Encefálica , Imageamento por Ressonância Magnética , Masculino , Malformações do Desenvolvimento Cortical/classificação , Malformações do Desenvolvimento Cortical/diagnóstico por imagem , Malformações do Desenvolvimento Cortical/cirurgia , Lobo Occipital/cirurgia , Estudos Retrospectivos , Adulto Jovem
11.
Histopathology ; 68(3): 378-87, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26040650

RESUMO

AIMS: To study three atypical glioneuronal tumours (GNTs), in order to shed light on the clinical and pathological features of this diverse tumour group. METHODS AND RESULTS: Clinical and neuropathological data for each case were retrospectively reviewed. Case 1 involved a 17-year-old boy with left leg movement difficulty. A mass lesion in the basal ganglia was detected radiologically; histopathological features included neurocytic/perivascular rosettes and a pilocytic astrocytoma component. Case 2 involved a 33-year-old man with intractable epilepsy. His left parietal lobe contained a cyst-like mass, resembling dysembryoplastic neuroepithelial tumour and rosette-forming glioneuronal tumour of the fourth ventricle microscopically. Case 3 involved a 21-year-old woman with a mass lesion in the mesencephalic tegmentum extending to the third and fourth ventricles and the suprasellar region. The lesion contained perivascular/neurocytic rosettes and an oligodendroglioma-like component. None of the tumours expressed an isocitrate dehydrogenase I mutation of the R132H type or contained a 1p/19q deletion, a BRAF(V600E) mutation, or KIAA1549-BRAF fusion. CONCLUSIONS: We describe three GNTs with atypical histopathology and locations. Additional cases and molecular studies are needed to better understand the biological nature of GNTs and to refine their classification system.


Assuntos
Astrocitoma/patologia , Neoplasias Encefálicas/patologia , Glioma/patologia , Neoplasias Neuroepiteliomatosas/patologia , Adolescente , Adulto , Astrocitoma/genética , Gânglios da Base/patologia , Neoplasias Encefálicas/genética , Feminino , Quarto Ventrículo/patologia , Glioma/genética , Humanos , Masculino , Neoplasias Neuroepiteliomatosas/genética , Lobo Parietal/patologia , Estudos Retrospectivos , Formação de Roseta , Adulto Jovem
12.
Yao Xue Xue Bao ; 51(3): 455-61, 2016 03.
Artigo em Zh | MEDLINE | ID: mdl-29859029

RESUMO

To investigate the effect that folic acid-modified polyrotaxanes(FPP) transfered siRNA CD47 to inhibit melanoma proliferation, the expression of CD47 in clinical melanoma patients was tested by Western blot and RT-PCR, respectively. Physical performance of FPP(siRNA-CD47: CD47) nanoparticles was tested by Malvern particle size instrument and scanning electron microscope. The clone formation experiment demonstrated that FPP(CD47) nanoparticles inhibited the growth of clones. Invasion assay revealed that FPP(CD47) inhibited migration of B16F10 cells. Tumor bearing mice were used in the experiment to test the efficacy of FPP(CD47) treatment. Compared with the control group, high expression of CD47 was observed in the clinical melanoma patients. FPP(CD47) nanoparticle size at 80 nm exhibited a potential of 10 m V; compared with FPP(Con), fluorescence intensity was significantly reduced to 4.2% and B16F10 cell clone formation was decreased by 91% in the FPP(CD47) treatment. Tumor volume of tumor-burdened mice was decreased by 90% with FPP(CD47) treatment. FPP(CD47) lowered CD47 protein and m RNA expression in the tumor. This study suggests that FPP may transfer siRNA CD47 into the cancer cells to inhibit melanoma growth effectively.


Assuntos
Antígeno CD47/uso terapêutico , Ácido Fólico/química , Melanoma/terapia , RNA Interferente Pequeno/uso terapêutico , Rotaxanos/química , Animais , Linhagem Celular Tumoral , Proliferação de Células , Vetores Genéticos , Humanos , Melanoma Experimental , Camundongos , Nanopartículas , Carga Tumoral
13.
Neuropathol Appl Neurobiol ; 41(3): 333-46, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24861831

RESUMO

AIMS: Angiocentric glioma (AG) is a rare, slow-growing tumour of the central nervous system. It is often associated with refractory epilepsy and occurs most commonly in children and young adults. We herein report nine cases of AG, including four with atypical histological findings. METHODS: The clinical data and clinicopathological findings of nine cases with AG histological features were described. RESULTS: All nine patients had a history of refractory epilepsy with a mean history of 4.4 years and a median age of 17.6 years at surgery. The AG lesions were located in the superficial cerebrocortical region. Histological examination of these cases revealed characteristic structural features of AG, including bipolar spindle-shaped cells with an angiocentric growth pattern. However, four cases also exhibited atypical histological features: one had astroblastoma-like characteristics, two had a distinct cystic region with an onion-like structure and myxoid changes, and the other one had a region involving many abnormal neurones reminiscent to ganglioglioma. All were positive for glial fibrillary acidic protein and vimentin. Eight cases were positive for epithelial membrane antigen (EMA), with a dot-like staining pattern. A diffuse D2-40 staining was visible in these cases, with two having similar staining pattern to EMA. All cases were immunonegative for BRAF V600E and isocitrate dehydrogenase-1 R132H mutations. CONCLUSIONS: Our results demonstrate that atypical histological features can be present in AG. A collection of more cases and further molecular analyses are required to confirm our findings.


Assuntos
Neoplasias Encefálicas/patologia , Glioma/patologia , Adolescente , Biomarcadores Tumorais/análise , Neoplasias Encefálicas/complicações , Criança , Pré-Escolar , Epilepsia/etiologia , Feminino , Glioma/complicações , Humanos , Imuno-Histoquímica , Imageamento por Ressonância Magnética , Masculino , Adulto Jovem
14.
Yi Chuan ; 37(11): 1160-6, 2015 11.
Artigo em Zh | MEDLINE | ID: mdl-26582530

RESUMO

The synaptonemal complex (SC) is a huge structure which assembles between the homologous chromosomes during meiotic prophase I. Drosophila germ cell-specific nucleoprotein C(2)M clustering at chromosomes can induce SC formation. To further study the molecular function and mechanism of C(2)M in meiosis, we constructed a bait vector for C(2)M and used the yeast two-hybrid system to identify C(2)M interacting proteins. Forty interacting proteins were obtained, including many DNA and histone binding proteins, ATP synthases and transcription factors. Gene silencing assays in Drosophila showed that two genes, wech and Psf1, may delay the disappearance of SC. These results indicate that Wech and Psf1 may form a complex with C(2)M to participate in the formation or stabilization of the SC complex.


Assuntos
Proteínas de Ciclo Celular/fisiologia , Proteínas de Drosophila/fisiologia , Saccharomyces cerevisiae/genética , Técnicas do Sistema de Duplo-Híbrido , Sequência de Bases , Proteínas de Ciclo Celular/genética , Biologia Computacional , Proteínas de Drosophila/genética , Dados de Sequência Molecular , Complexo Sinaptonêmico/fisiologia
15.
Nanotechnology ; 25(41): 415501, 2014 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-25248862

RESUMO

Convenient and simultaneous detection of multiple biomarkers such as DNA and proteins with biocompatible materials and good analytical performance still remains a challenge. Herein, we report the respective and simultaneous detection of DNA and bovine α-thrombin (thrombin) entirely based on biocompatible carbon materials through a specially designed fluorescence on-off-on process. Colorful fluorescence, high emission efficiency, good photostability and excellent compatibility enables graphene quantum dots (GQDs) as the best choice for fluorophores in bioprobes, and thus two-colored GQDs as labeling fluorophores were chemically bonded with specific oligonucleotide sequence and aptamer to prepare two probes targeting the DNA and thrombin, respectively. Each probe can be assembled on the graphene oxide (GO) platform spontaneously by π-π stacking and electrostatic attraction; as a result, fast electron transfer in the assembly efficiently quenches the fluorescence of probe. The presence of DNA or thrombin can trigger the self-recognition between capturing a nucleotide sequence and its target DNA or between thrombin and its aptamer due to their specific hybridization and duplex DNA structures or the formation of apatamer-substrate complex, which is taken advantage of in order to achieve a separate quantitative analysis of DNA and thrombin. A dual-functional biosensor for simultaneous detection of DNA and thrombin was also constructed by self-assembly of two probes with distinct colors and GO platform, and was further evaluated with the presence of various concentrations of DNA and thrombin. Both biosensors serving as a general detection model for multiple species exhibit outstanding analytical performance, and are expected to be applied in vivo because of the excellent biocompatibility of their used materials.


Assuntos
Técnicas Biossensoriais/métodos , DNA/análise , Grafite , Pontos Quânticos , Trombina/análise , Animais , Bovinos , Corantes Fluorescentes
16.
Int J Gynecol Cancer ; 24(3): 506-12, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24557435

RESUMO

OBJECTIVE: This study aimed to determine the clinical prognostic factors involved in carcinosarcoma of the ovary, fallopian tube, and peritoneum. MATERIALS AND METHODS: This retrospective study was undertaken by the Taiwanese Gynecologic Oncology Group. The retrieved clinical data included demographic characteristics, medical disease, tumor status, extent of surgery, and adjuvant chemotherapy. RESULTS: In total, 63 patients with carcinosarcoma of the ovary, fallopian tube, and peritoneum were identified. Sixty-one patients with complete data were enrolled for further data analysis. The mean follow-up period was 1.0 year, and the mean overall survival was 15.4 months. By log-rank tests, age, menopausal status, parity, hypertension, diabetes, primary tumor size, para-aortic lymph node metastasis, pretreatment CA-125, preceding diagnostic surgery, hysterectomy, lymphadenectomy, other surgeries, and paclitaxel use were not predictive of overall survival.Omentectomy, no gross residual implants after surgery, platinum treatment, and no pelvic lymph node metastasis had a trend toward better survival. Early diagnosis at stage I and cisplatin/ifosfamide regimen were significant associated with a better overall survival in log-rank and simple Cox regression tests. Bilateral ovarian tumors and metastatic tumors larger than 2 cm were significantly associated with a poorer overall survival. CONCLUSIONS: Early diagnosis at stage I, unilateral ovarian tumor, metastatic tumors less than 2 cm, and cisplatin/ifosfamide regimen were predictive of a better survival.Omentectomy and complete debulking surgery also showed a trend toward better survival. Thus, these treatment strategies should be applied in patients with carcinosarcoma of the ovary, fallopian tube, and peritoneum.


Assuntos
Carcinossarcoma/mortalidade , Neoplasias das Tubas Uterinas/mortalidade , Neoplasias Ovarianas/mortalidade , Neoplasias Peritoneais/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinossarcoma/diagnóstico , Carcinossarcoma/terapia , Neoplasias das Tubas Uterinas/diagnóstico , Neoplasias das Tubas Uterinas/terapia , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/terapia , Neoplasias Peritoneais/diagnóstico , Neoplasias Peritoneais/terapia , Prognóstico , Estudos Retrospectivos , Taiwan/epidemiologia , Adulto Jovem
17.
Proc Natl Acad Sci U S A ; 108(16): 6399-404, 2011 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-21444818

RESUMO

China and other rapidly developing economies face the dual challenge of substantially increasing yields of cereal grains while at the same time reducing the very substantial environmental impacts of intensive agriculture. We used a model-driven integrated soil-crop system management approach to develop a maize production system that achieved mean maize yields of 13.0 t ha(-1) on 66 on-farm experimental plots--nearly twice the yield of current farmers' practices--with no increase in N fertilizer use. Such integrated soil-crop system management systems represent a priority for agricultural research and implementation, especially in rapidly growing economies.


Assuntos
Agricultura/métodos , Produtos Agrícolas/crescimento & desenvolvimento , Abastecimento de Alimentos , Solo , Zea mays/crescimento & desenvolvimento , Agricultura/economia , China , Produtos Agrícolas/economia , Fertilizantes/economia
18.
ScientificWorldJournal ; 2014: 745640, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25140346

RESUMO

Decision tree is one of the famous classification methods in data mining. Many researches have been proposed, which were focusing on improving the performance of decision tree. However, those algorithms are developed and run on traditional distributed systems. Obviously the latency could not be improved while processing huge data generated by ubiquitous sensing node in the era without new technology help. In order to improve data processing latency in huge data mining, in this paper, we design and implement a new parallelized decision tree algorithm on a CUDA (compute unified device architecture), which is a GPGPU solution provided by NVIDIA. In the proposed system, CPU is responsible for flow control while the GPU is responsible for computation. We have conducted many experiments to evaluate system performance of CUDT and made a comparison with traditional CPU version. The results show that CUDT is 5 ∼ 55 times faster than Weka-j48 and is 18 times speedup than SPRINT for large data set.


Assuntos
Algoritmos , Árvores de Decisões , Simulação por Computador , Mineração de Dados/métodos
19.
Talanta ; 273: 125945, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38508124

RESUMO

Few study has been carried out on the construction of immunesensors utilized the photoelectric and catalytic signal of nanomaterial. Here, a dual-signal electrochemical immunosensor was constructed for procalcitonin (PCT) detection based on the excellent photoelectric and hydrogen evolution performance of molybdenum-doped cobalt-iron sulfur nanosheets modified by platinum nanoparticles (Pt/Mo-CoFeS). Due to the electronic structure regulation between Pt and Mo-CoFeS, Pt/Mo-CoFeS exhibits superior photoelectric and hydrogen evolution performance compared to single Mo-CoFeS, which improved the sensitivity of the electrochemical immunosensor. Furthermore, the presence of Pt improves surface area and biocompatibility, achieving more antibodies loading and signal amplification. The linear range of PCT detection are 0.002-20 ng mL-1 and 0.002-50 ng mL-1, the detection limits are 0.0015 and 0.0012 ng mL-1. In addition, this electrochemical immunosensor was applied to the PCT analysis in human serum samples with high recoveries. F-test and t-test show that there is no significant difference in the test results between the HER and photoelectric signals, the mutual verification between above two signals can effectively improve the accuracy of detection result.


Assuntos
Técnicas Biossensoriais , Grafite , Nanopartículas Metálicas , Nanocompostos , Humanos , Pró-Calcitonina , Técnicas Eletroquímicas/métodos , Nanopartículas Metálicas/química , Técnicas Biossensoriais/métodos , Imunoensaio/métodos , Nanocompostos/química , Platina/química , Grafite/química , Limite de Detecção , Ouro/química
20.
Bioelectrochemistry ; 160: 108758, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38878459

RESUMO

For the electrodeposition, the conductivity and lattice structure of substrate is important to the morphology and lattice of the deposited material. In this study, gold-platinum (AuPt) nanopartical was deposited on nickel foam (NF) based on the lattice induced orientation of the Ni substrate, and the obtained AuPt/NF was applied to construct electrochemical impedimetric immunosensor for procalcitonin (PCT) detection. As a new immunosensor matrix, NF with higher electrical conductance, flexibility and specific surface area, which can improve the plasticity, sensitivity and universality of the immunoelectrode. Due to the lattice matching between Au and Ni, ultrathin AuPt nanolayer with good biocompatibility and large surface area can be modified on the NF surface, which can bind more biomolecules and amplifies the change of impedance signal. Based on the synergistic effect between AuPt and NF, PCT detection based on this electrochemical impedimetric immunosensor with a wide linear range (0.2 pg mL-1 to 20 ng mL-1) and low detection limit (0.11 pg mL-1). In addition, this impedimetric immunosensor exhibits high recovery in the PCT detection of serum samples. This work provides a new thought and method for the construction of electrochemical immunosensor.

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