Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 91
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Sci Total Environ ; 711: 135184, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32000351

RESUMO

6-Hydroxy-BDE-47 (6-OH-BDE-47) is an important in vivo metabolite derived from 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), a ubiquitous environmental pollutant. The chemical has been widely detected in environmental and biological samples. However, as a potential neurotoxin, whether 6-OH-BDE-47 could promote the development of typical neurodegenerative diseases such as Parkinson's disease (PD) is still unknown. Here, we tested the potential PD-related neurotoxic effect of 6-OH-BDE-47 in rat. The chemical with levels of 0.1, 1 and 10 µg was stereotaxically injected into the right midbrain regions of rat where contain abundant dopaminergic neurons. The resulting deteriorated motor function and decreased levels of striatal dopamine and nigrostriatal tyrosine hydroxylase indicate the dopaminergic neuron loss after the injection. Proteomics study revealed that protein degradation pathways were affected. Western blot analysis confirmed that 6-OH-BDE-47 could inhibit ubiquitination and autophagy, resulting in the increased formation of α-synuclein (α-syn) aggregate, an important pathological hallmark of PD. Overall, our study demonstrated that the 6-OH-BDE-47 administration could induce motor defect by impairing dopaminergic system and promote α-syn aggregation by inhibiting ubiquitination and autophagy, suggesting that the occurrence of 6-OH-BDE-47 in brain could be a risk for developing PD.


Assuntos
Doença de Parkinson , Animais , Neurônios Dopaminérgicos , Bifenil Polibromatos , Ratos , Ratos Sprague-Dawley , alfa-Sinucleína
2.
J Neurotrauma ; 37(1): 43-54, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31397209

RESUMO

Microglia are the primary immune cells in the central nervous system and undergo significant morphological and transcriptional changes after traumatic brain injury (TBI). However, their exact contribution to the pathogenesis of TBI is still debated and remains to be elucidated. In the present study, thy-1 GFP mice received a colony-stimulating factor 1 receptor inhibitor (PLX3397) for 21 consecutive days, then were subjected to moderate fluid percussion injury (FPI). Brain samples were collected at 1 day and 3 days after FPI for flow cytometry analysis, immunofluorescence, dendrite spine quantification, terminal deoxynucleotidyl transferase dUTP nick end labeling assay, and Western blot. We found that PLX3397 treatment significantly attenuated the percentages of resident microglia and infiltrated immune cells. Depletion of microglia promoted neurite outgrowth, preserved dendritic spines and reduced total brain cell and neuronal apoptosis after FPI, which was accompanied by decreased the protein levels of endoplasmic reticulum stress marker proteins, C/EBP-homologous protein and inositol-requiring kinase 1α. Taken together, these findings suggest that microglial depletion may exert beneficial effects in the acute stage of FPI.

3.
Curr Neurovasc Res ; 16(4): 335-339, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31612832

RESUMO

BACKGROUND: Single Nucleotide Polymorphisms (SNPs) in the Erythropoietin (EPO) promoter region have been shown to influence EPO protein expression, and high blood levels of EPO are associated with an increased risk of brain injury in very preterm infants. Here, we investigated the genotype distributions and association of three EPO gene polymorphisms (rs1617640, rs551238, and rs507392) with the risk of brain injury in preterm infants. METHODS: 304 preterm infants with a gestational age of 28 to 34 weeks were enrolled in this study. Brain injury was evaluated by brain ultrasound and MRI examination. EPO gene Single- Nucleotide Polymorphisms (SNPs) were genotyped by the Agena MassARRAY system, and their association with brain injury susceptibility in preterm infants was analyzed. RESULTS: EPO polymorphism rs551238 showed a significant difference in the genotypic distributions between the brain injury group and the control group, and was significantly correlated with reduced susceptibility to brain injury in preterm infants according to the results obtained from both the additive model (OR = 0.520, 95% CI: 0.339-0.799, P = 0.003) and the dominant model (OR = 0.523, 95% CI: 0.332-0.853, P = 0.009). EPO polymorphisms rs1617640 and rs507392 did not meet the Hardy-Weinberg equilibrium in the study population (P < 0.05) and were, thus, not subjected to further analysis for their impacts on brain injuries. CONCLUSION: The "C" allele of rs551238 was correlated with a reduced risk of brain injury in preterm infants which may serve as a potential marker for brain injury prediction in preterm infants.

4.
Cell Mol Neurobiol ; 39(8): 1151-1163, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31270712

RESUMO

Ischemic stroke often causes motor and cognitive deficits. Deregulated glia gap junction communication, which is reflected by increased protein levels of glial fibrillary acidic protein (GFAP) and connexin 43 (Cx43), has been observed in ischemic hippocampus and has been associated with cognitive impairment in animal stroke models. Here, we tested the hypothesis that reactive astrocytes-mediated loss of synaptophysin (SYP) and CREB-regulated transcription coactivator 1 (CRTC1) contribute to dysfunction in glia gap junction communication and memory impairment after ischemic stroke. Male Sprague-Dawley rats were subjected to a 90-min middle cerebral artery occlusion (MCAO) with 7-day reperfusion. Fluorocitrate (1 nmol), the reversible inhibitor of the astrocytic tricarboxylic acid cycle, was injected into the right lateral ventricle of MCAO rats once every 2 days starting immediately before reperfusion. The Morris water maze was used to assess memory in conjunction with western blotting and immunostaining to detect protein expression and distribution in the hippocampus. Our results showed that ischemic stroke caused significant memory impairment accompanied by increased protein levels of GFAP and Cx43 in hippocampal tissue. In addition, the levels of several key memory-related important proteins including SYP, CRTC1, myelin basic protein and high-mobility group-box-1 were significantly reduced in the hippocampal tissue. Of note, inhibition of reactive astrocytes with fluorocitrate was shown to significantly reverse the above noted changes induced by ischemic stroke. Taken together, our findings demonstrate that inhibiting reactive astrocytes with fluorocitrate immediately before reperfusion may protect against ischemic stroke-induced memory impairment through the upregulation of CRTC1 and SYP.


Assuntos
Astrócitos/metabolismo , Citratos/farmacologia , Aprendizagem/efeitos dos fármacos , Transtornos da Memória/fisiopatologia , Acidente Vascular Cerebral/metabolismo , Sinaptofisina/metabolismo , Fatores de Transcrição/genética , Regulação para Cima/efeitos dos fármacos , Animais , Astrócitos/efeitos dos fármacos , Isquemia Encefálica/patologia , Isquemia Encefálica/fisiopatologia , Conexina 43/metabolismo , Proteína Glial Fibrilar Ácida/metabolismo , Proteína HMGB1/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Masculino , Atividade Motora/efeitos dos fármacos , Proteína Básica da Mielina/metabolismo , Ratos Sprague-Dawley , Acidente Vascular Cerebral/fisiopatologia , Fatores de Transcrição/metabolismo
5.
Acta Histochem ; 121(6): 704-711, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31235073

RESUMO

Cataract, opacification of the lens, is one of the most important reasons of visual impairment and blindness. Though microRNAs (miRNAs) have been demonstrated to play important roles in cataractogenesis, the underlying molecular mechanisms in this progress remain obscure. In the present study, microRNA-23b-3p (miR-23b) overexpression promoted the proliferation, migration and epithelial-mesenchymal transition (EMT), whereas miR-23b knockdown markedly inhibited the proliferation, migration and TGF-ß-induced EMT of lens epithelial cells (LECs). In TGF-ß-induced LECs, the expression of miR-23b was markedly upregulated and the expression of Sprouty2 (SPRY2) was markedly downregulated, furthermore the mRNA and protein levels of SPRY2 were markedly decreased in miR-23b inhibitor-transfected LECs. We then performed a Dual-luciferase reporter assay to confirm that miR-23b directly targeted SPRY2. The promoted migration and EMT of LECs by enforced expression of miR-23b were suppressed by SPRY2 overexpression. The findings present the first evidence indicating that miR-23b can promote the proliferation, migration, and EMT of LECs by targeting SPRY2 and the inhibition of miR-23b may possess the therapeutic potential for cataract.


Assuntos
Movimento Celular , Proliferação de Células , Células Epiteliais/metabolismo , Transição Epitelial-Mesenquimal , Proteínas do Olho/metabolismo , Cristalino/metabolismo , MicroRNAs/metabolismo , Catarata/genética , Catarata/metabolismo , Catarata/patologia , Linhagem Celular , Células Epiteliais/patologia , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Cristalino/patologia , Proteínas de Membrana/genética , MicroRNAs/genética
6.
Phytother Res ; 33(6): 1736-1747, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31006910

RESUMO

Glioblastoma multiforme (GBM) is a highly aggressive type of brain tumour. Patients with GBM respond poorly to chemotherapy and have poor survival outcomes. Neuron-glial antigen 2 (NG2), also known as chondroitin sulphate proteoglycan 4 (CSPG4), has been shown to contribute to critical processes, such as cell survival, proliferation, and chemotherapy resistance, during glioma progression. In this study, we found that furanodienone (FUR), a diene-type sesquiterpene isolated from the rhizomes of Rhizoma curcumae, exhibited a potential cytotoxic effect on temozolomide (TMZ)-resistant GBM cells in vitro by inhibiting CSPG4 and related signalling pathways. Studies investigating the mechanism demonstrated that FUR suppressed CSPG4-Akt-ERK signalling, inflammatory responses, and cytokine levels but activated caspase-dependent pathways and mitochondrial dysfunction. Furthermore, an immunofluorescence assay and a dual-luciferase reporter assay revealed that inhibition of EGR1-mediated transcription might have contributed to the FUR-dependent blockade of CSPG4 signalling and glioma cell survival. These results established a link between FUR-induced CSPG4 inhibition and the suppression of EGR1-dependent transcription. Attenuation of ERK1/2 and cytokine signalling might have generated the EGR1-dependent negative feedback loop of the CSPG4 pathway during FUR-induced apoptosis. These findings suggested that FUR could be a therapeutic candidate for the treatment of malignant glioma via targeting CSPG4 signalling.


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Proteína 1 de Resposta de Crescimento Precoce/fisiologia , Furanos/farmacologia , Glioblastoma/tratamento farmacológico , Sesquiterpenos/farmacologia , Temozolomida/uso terapêutico , Adulto , Apoptose/efeitos dos fármacos , Apoptose/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Proteoglicanas de Sulfatos de Condroitina/genética , Proteoglicanas de Sulfatos de Condroitina/metabolismo , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Resistencia a Medicamentos Antineoplásicos/genética , Furanos/administração & dosagem , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glioblastoma/genética , Glioblastoma/patologia , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sesquiterpenos/administração & dosagem , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Temozolomida/administração & dosagem , Transcrição Genética/efeitos dos fármacos
7.
Brain Behav ; 9(4): e01248, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30834702

RESUMO

BACKGROUND: Mild hypothermia is wildly used in clinical treatment of traumatic brain injury (TBI). However, the effect of mild hypothermia on endoplasmic reticulum (ER) stress-induced apoptosis after severe TBI is still unknown. METHODS: In the present study, we used BALB/c mice to investigate the efficacy of posttraumatic mild hypothermia in reducing ER stress. Severe TBI was induced by controlled cortical impact injury. Mild hypothermia treatment was performed immediately after surgery and maintained for 4 hr. The animals were euthanized at 1 and 7 days after severe TBI. The expression levels of ER stress marker proteins were evaluated using Western blot and immunofluorescence. Cell apoptosis rate was analyzed by TUNEL staining. Neuronal functions of the mice were assessed using rotarod test and Morris water maze. RESULTS: Our results revealed that mild hypothermia significantly attenuated ER stress marker proteins, including p-eIF2α/eIF2α, ATF4, CHOP and IRE-1α, and reduced apoptosis rate in the pericontusion region at 1 and 7 days after severe TBI. Interestingly, mild hypothermia also prevented the translocation of CHOP into nucleus. In addition, posttraumatic mild hypothermia significantly improved neuronal functions after severe TBI. CONCLUSIONS: Our findings illustrated that mild hypothermia could reduce ER stress-induced apoptosis and improve neuronal functions after severe traumatic brain injury.


Assuntos
Apoptose/fisiologia , Lesões Encefálicas Traumáticas/metabolismo , Estresse do Retículo Endoplasmático/fisiologia , Hipotermia Induzida/métodos , Neurônios/metabolismo , Animais , Encéfalo/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Ratos , Ratos Sprague-Dawley
8.
Front Cell Neurosci ; 13: 61, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30886573

RESUMO

Aggregated amyloid-ß protein (Aß) and Aß-induced neuronal apoptosis have been implicated as critical factors in the pathophysiology of Alzheimer's disease (AD). Certain preclinical results have indicated that the increased accumulation of protein aggregates in AD-affected neurons activates the unfolded protein response (UPR), a pathological phenomenon, which predominantly mediates the aberrant endoplasmic reticulum (ER) stress and apoptotic cascades in neuronal cells. In the present study, we confirmed that Santacruzamate A (STA, a natural product isolated from a Panamanian marine cyanobacterium) attenuates Aß protein fragment 25-35 (Aß25-35)-induced toxicity in PC12 cells and rescues cognitive deficits in APPswe/PS1dE9 mice by enhancing ER stress tolerance. We first demonstrated the anti-apoptotic effects of STA by evaluating caspase-3 activity, annexin V/propidium iodide (PI) staining, and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Behavioral testing of STA-treated APPswe/PS1dE9 mice showed that the pronounced memory impairments were ameliorated and that the consolidated memories were stably maintained over a 2-week period. The mechanistic studies provided evidence that STA inhibited Aß25-35-induced UPR and ER stress by regulating the ER retention signal (KDEL) receptor, which reinforced the retention of resident chaperones in the ER lumen. Furthermore, STA regulated the expression of the mitochondrial intermembrane space assembly protein 40 (Mia40) and augmenter of liver regeneration (ALR), which ultimately attenuated the mitochondrial fission and apoptosis pathways. Together, our present findings suggest that the KDEL receptor and Mia40-ALR play a role in mitigating Aß25-35-induced neurotoxicity, which might in turn positively regulate learning and memory. These observations support that STA may be a promising agent for reversing the progression of AD.

9.
Cell Biol Int ; 43(2): 125-135, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30288851

RESUMO

Alternatively activated (M2) macrophage promotes glioma progression and immune escape as the most immunocyte in glioma microenvironment. Finding out the key protein regulating M2 macrophage polarization is necessary for improving treatment. Whether immunity related GTPase M (IRGM) is involved in glioma development and M2 macrophage polarization is unknown. IRGM and M2 macrophage marker CD206 expression were examined using immunohistochemistry among 35 glioma and 11 non-cancerous brain specimens. We found IRGM scores were positively correlated with CD206 scores in glioma specimens and monocyte proportion in blood samples. A172 glioma cells transfected with either IRGM knock-down lentivirus (Lenti-IRGM) or control lentivirus (Lenti-HK) were subcutaneously injected into nude mice. In vivo, xenografted glioma size of the Lenti-IRGM group was smaller and had weaker fluorescence signal than Lenti-HK control group. Immunofluorescence results showed that there was obviously decreased IRGM, CD206, and IL-8 expression in the mice glioma of Lenti-IRGM group than Lenti-HK control group. In vitro, flow cytometry results showed that M2 polarization from THP-1 cocultured with Lenti-IRGM glioma cells decreased in contrast to that with Lenti-HK glioma cells; there were less interleukin-8 (IL-8) and macrophage inflammation protein 3-α (MIP-3α), but more interleukin-6 (IL-6) in the supernatant of Lenti-IRGM glioma cells than matched control. Western blot and immunofluorescence displayed that IRGM strongly promoted sequestosome-1 (p62/SQSTM1), necrosis factor receptor-activating factor 6 (TRAF6) expression and NF-κB transportation to the nucleus. Realtime PCR results demonstrated IRGM also promoted NF-κB downstream cytokines IL-8 and MIP-3α mRNA expression. These data suggested that IRGM could promote glioma development and M2 macrophage polarization by regulating p62/TRAF6/NF-κB pathway-mediated IL-8 production.


Assuntos
Proteínas de Ligação ao GTP/metabolismo , Glioma/patologia , Interleucina-8/metabolismo , NF-kappa B/metabolismo , Proteína Sequestossoma-1/metabolismo , Fator 6 Associado a Receptor de TNF/metabolismo , Animais , Linhagem Celular , Polaridade Celular , Técnicas de Cocultura , Proteínas de Ligação ao GTP/antagonistas & inibidores , Proteínas de Ligação ao GTP/genética , Glioma/metabolismo , Humanos , Interleucina-8/genética , Macrófagos/citologia , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Transplante Heterólogo
10.
Pathol Res Pract ; 215(1): 90-96, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30391210

RESUMO

Glioma is the commonest malignant tumor in the central nervous system (CNS), characterized by rapid growth. However, the molecular mechanism underlying the growth remains unclear. Immunity-related GTPase family M protein (IRGM) participates in immune response to pathogen and tumorigenesis. Proliferation and autophagy are two crucial functions contributing to aggressive growth. Therefore, our aims were to probe whether IRGM regulates glioma proliferation and autophagy. In this study, we found that 47 glioma specimens had more IRGM expression than 11 non-cancerous brain tissues with immunohistochemistry. IRGM was also up-regulated in human glioma cell lines U87, U251 and A172 and so on compared with immortalized astrocytes. Importantly, overexpression of IRGM significantly increased the cell colonies formation, cell proliferation and Akt activation (Thr308 and Ser473 sites) than matched control. On another hand, all of IRGM, autophagy marker LC3II and autophagy adaptor p62 gradually increased after starvation 2 and 4 h. Furthermore, western blot and immunofluorescence results showed that knockdown of IRGM inhibited the formation of LC3-II and the expression of p62. Our data uncovered that IRGM acted in glioma proliferation and autophagy, providing a new target with dual roles for the future translation research.


Assuntos
Autofagia/fisiologia , Proliferação de Células/fisiologia , GTP Fosfo-Hidrolases/metabolismo , Glioma/metabolismo , Linhagem Celular Tumoral , Técnicas de Silenciamento de Genes/métodos , Glioma/patologia , Humanos , Regulação para Cima
11.
J Cell Biochem ; 2018 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-30485520

RESUMO

Diabetic retinopathy (DR) is a leading cause of adult visual impairment and loss. This study aims to explore the effects of microRNA-9 (miR-9) on retinal neovascularization during DR by targeting the vascular endothelial growth factor A (VEGFA). DR rat models were successfully established. Retinal microvascular endothelial cells (RMECs) of DR rats were isolated and treated with miR-9 mimic, miR-9 inhibitor or small interfering RNA (siRNA)-VEGFA. The expressions of miR-9, VEGFA, and cluster of differentiation 31 (CD31) of the rats' tissues and cells were examined. The targeting relationship between miR-9 and VEGFA was testified. The tubule formation, the cell proliferation and the periodic distribution and apoptosis were evaluated after transfection. In the retinal tissues of DR rats, miR-9 expression decreased while the expression of VEGFA and CD31 increased. Notably, miR-9 targeted and inhibited VEGFA expression. In response to the treatment of miR-9 mimic and siRNA-VEGFA, a reduction was identified in CD31 expression, tubule formation, and proliferation of RMECs and cell ratio in the S phase, but an increase was observed in apoptosis rate of RMECs. The treatment of miR-9 inhibitor reversed the manifestations. Our study demonstrated that miR-9 could inhibit retinal neovascularization of DR and tubule formation, and promote apoptosis in RMECs by targeting VEGFA.

12.
J Comput Chem ; 39(24): 1979-1989, 2018 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-30315587

RESUMO

On the example of an aggregate of two perylenebisimide (PBI) molecules the character of the lowest excited electronic states in terms of charge transfer (CT) and Frenkel exciton (FE) configurations is investigated as a function of the intermolecular arrangement. A minimal model Hamiltonian based on two FE and two CT configurations at the frontier-orbitals CIS (FOCIS) level is shown to represent a simple and comprehensible approach providing insight into the physical significance of the model Hamiltonian matrix elements. The recently introduced analysis and diabatization procedure (Liu et al., J. Chem. Phys. 2015, 143, 084106 ) method is used to extract the energies of the configurations and their interactions (the model Hamiltonian parameters) also from the accurate CC2 approach. An analysis in terms of diabatic energy profiles and their interactions shows that the FOCIS parameters give a qualitatively correct description of the adiabatic excited state energy profiles. Comparison with CC2 reveals, however, the presence of avoided crossings at FOCIS level, associated with a large character change (CT/FE) of the excited states as a function of the aggregate structure, which represents the major drawback of FOCIS results. We show that proper amendment of the FOCIS-derived parameters allows to accurately represent the potential energy surfaces and crossings of the excited dimer states as a function of the aggregate structure. © 2018 Wiley Periodicals, Inc.

13.
Cell Physiol Biochem ; 48(3): 1088-1098, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30041238

RESUMO

BACKGROUND/AIMS: To investigate the mechanism that enables oxidative stress and cytoskeleton protein carbonylation to contribute to axonal dysfunction in traumatic brain injury (TBI). METHODS: We created an in vitro model of neuronal oxidative damage by exposing a neuron-like cell line (PC-12) to different concentrations (100 µM, 200 µM, and 300 µM) of H2O2 for 24 h or 48 h. Carbonyl modification of cytoskeletal proteins (ß-actin and ß-tubulin) and its impact on ß-actin/ß-tubulin filament dynamics were determined by enzyme-linked immunosorbent assay, immunostaining, and western blotting. Depolymerization of ß-actin/ß-tubulin filaments was evaluated using the monomer/polymer ratio of each protein via western blotting. Phosphorylation of the neurofilament heavy chain (P-NFH) was used as an axonal injury marker and detected by immunostaining. RESULTS: Our results showed that H2O2 treatment led to increased oxidative stress in PC-12 cells, as indicated by the increased generation of malondialdehyde and 8-hydroxydeoxyguanosine and decreased intracellular glutathione levels. H2O2 treatment also increased carbonyl modification of total proteins and cytoskeleton proteins ß-actin/ß-tubulin, which occurred concurrently with the suppression of proteasome activity. Moreover, H2O2 treatment increased the generation of the axonal injury marker P-NFH, and depolymerization of the ß-actin/ß-tubulin filaments was indicated by increased monomer/polymer ratios of each protein. Lastly, overexpression of the proteasome ß5 subunit in PC-12 cells significantly reduced the H2O2-induced accumulation of carbonylated ß-actin/ ß-tubulin, P-NFH, and ß-actin/ß-tubulin depolymerization. CONCLUSIONS: We concluded that carbonylation of cytoskeleton proteins could lead to depolymerization of their filaments and axonal injury, and proteasome suppression contributes to the accumulation of carbonylated proteins under oxidative conditions.


Assuntos
Citoesqueleto de Actina/efeitos dos fármacos , Proteínas do Citoesqueleto/metabolismo , Peróxido de Hidrogênio/farmacologia , Carbonilação Proteica/efeitos dos fármacos , Citoesqueleto de Actina/metabolismo , Animais , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Glutationa/metabolismo , Malondialdeído/metabolismo , Proteínas de Neurofilamentos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Células PC12 , Fosforilação/efeitos dos fármacos , Complexo de Endopeptidases do Proteassoma/genética , Complexo de Endopeptidases do Proteassoma/metabolismo , Subunidades Proteicas/genética , Subunidades Proteicas/metabolismo , Ratos , Tubulina (Proteína)/metabolismo
14.
Cancer Sci ; 109(9): 2651-2659, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29949235

RESUMO

Glioma is the most common central nervous system tumor and associated with poor prognosis. Identifying effective diagnostic biomarkers for glioma is particularly important in order to guide optimizing treatment. MicroRNAs (miRNAs) have drawn much attention because of their diagnostic value in diverse cancers, including glioma. We summarized studies to identify the potential diagnostic values of miRNAs in glioma patients. We included articles reporting miRNAs for differentiation of glioma patients from controls. We calculated sensitivities, specificities, and area under the curves (AUC) of individual miRNA and miRNA panels. We found that overall sensitivity, specificity, and AUC of miRNAs in diagnosis of glioma were 85% (95% confidence interval [CI]: 0.81-0.89), 90% (95% CI 0.85-0.93), and 93% (95% CI 0.91-0.95), respectively. Meta-regression analysis showed that the detection of miRNAs expression in cerebrospinal fluid (CSF) and brain tissue largely improved the diagnostic accuracy. Likewise, panels of multiple miRNAs could enhance the pooled sensitivity. Moreover, AUC of miR-21 was 0.88, with 86% sensitivity and 94% specificity. This study demonstrated that miRNAs could function as potential diagnosis markers in glioma. Detection of miRNAs in CSF and brain tissue displays high accuracy in the diagnosis of glioma.


Assuntos
Biomarcadores Tumorais/líquido cefalorraquidiano , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Glioma/diagnóstico , Glioma/genética , MicroRNAs/líquido cefalorraquidiano , MicroRNAs/genética , Encéfalo/patologia , Humanos , Sensibilidade e Especificidade
15.
Gene ; 668: 77-86, 2018 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-29777909

RESUMO

BACKGROUND: An increasing number of studies have shown that long noncoding RNAs (lncRNAs) play important roles in the development of glioma. However, a systematic review and meta-analysis to evaluate the clinical value of lncRNA expression in glioma patients is lacking. We performed this study to assess the relationship between the expression of various lncRNAs and the clinicopathological features, diagnosis and prognosis of glioma. MATERIALS AND METHODS: Eligible studies were identified through a comprehensive literature search. We conducted a subgroup analysis to assess the clinicopathological value of urothelial carcinoma associated 1 (UCA1). Pooled hazard ratios (HRs) of lncRNAs for survival were calculated to analyze the prognostic performance of lncRNAs. RESULTS: In total, 40 studies, including 30 investigating clinicopathological features, 3 investigating diagnoses and 32 investigating prognoses, were analyzed in this study. UCA1 expression was positively associated with tumor size (odds ratio [OR], 2.09; 95% confidence interval [CI], 1.06-4.15; P < 0.001) and World Health Organization (WHO) grade (OR, 3.84, [95% CI 1.84-8.01], P < 0.001). In the prognostic meta-analysis, high metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) expression could predict poor overall survival (OS) in patients with glioma, with a pooled HR of 2.32 (95% CI: 1.64-3.27, P < 0.001). CONCLUSIONS: This systematic review and meta-analysis demonstrated that lncRNAs are associated with tumor size, WHO grade, and prognosis in glioma patients. lncRNAs could function as potential molecular biomarkers of the clinicopathology and prognosis of glioma.


Assuntos
Neoplasias Encefálicas/diagnóstico , Glioma/diagnóstico , RNA Longo não Codificante/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Glioma/genética , Glioma/metabolismo , Glioma/patologia , Humanos , Prognóstico
16.
Pharmacogenet Genomics ; 28(5): 117-124, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29642234

RESUMO

BACKGROUND: Hyperuricemia and gout have become increasingly prevalent in China. Allopurinol is an effective urate-lowering therapy, but it has severe side effects. HLA-B*5801 is highly associated with the allopurinol-induced toxic epidermal necrolysis and Stevens-Johnson syndrome. PATIENTS AND METHODS: In this retrospective report, we had genotyped HLA-B*5801 in 253 cases of hyperuricemia and gout patients in a Han population in Shenzhen and analyzed the clinical management of medications. RESULTS: We found 30 carriers of the HLA-B*5801 allele in 253 cases of hyperuricemia or gout patients in the population (11.9%). Allopurinol was prescribed in both HLA-B*5801-positive and HLA-B*5801-negative groups. The evaluation of four models with or without genetic screening and management of allopurinol or febuxostat indicated that the HLA-B*5801 screening had significant cost benefit for clinical management. CONCLUSION: For appropriate management and cost-effectiveness, the HLA-B*5801 allele should be screened in all patients with hyperuricemia and gout in the Chinese population.


Assuntos
Alopurinol/uso terapêutico , Febuxostat/uso terapêutico , Supressores da Gota/uso terapêutico , Gota/genética , Antígenos HLA-B/genética , Hiperuricemia/genética , Adulto , Alopurinol/economia , China/etnologia , Análise Custo-Benefício , Febuxostat/economia , Feminino , Frequência do Gene , Testes Genéticos/economia , Gota/tratamento farmacológico , Gota/etnologia , Supressores da Gota/economia , Humanos , Hiperuricemia/tratamento farmacológico , Hiperuricemia/etnologia , Masculino , Pessoa de Meia-Idade , Medicina de Precisão , Estudos Retrospectivos , Resultado do Tratamento
17.
DNA Cell Biol ; 37(2): 78-89, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29265876

RESUMO

Technological advancements in next-generation sequencing are continually changing the landscape of genomic, transcriptomic, and epigenetic research at the single-cell level. These technologies have been used to detect and analyze circulating tumor cells (CTCs) at the molecular level and provide a new approach for the management of cancer patients. A series of unanticipated discoveries, including the heterogeneity of cancer cell populations, new driver mutations responsible for the resistance of tumors to chemotherapy, and the mechanism of tumor metastasis, have been made using single CTC sequencing. CTC detection has been used in cancer diagnosis and monitoring and in determining the prognosis of cancer patients. Traditional treatment for cancer patients is universal and does not consider genetic variations among patients, but in the era of precision medicine, giving the right drug to the right patient at the right time is the core philosophy. In this study, we review the fundamental principles of CTC isolation and single-cell sequencing and discuss recent progress in their application in both basic research and clinical fields and describe the current challenges.


Assuntos
Neoplasias/patologia , Células Neoplásicas Circulantes/efeitos dos fármacos , Análise de Célula Única , Animais , Antineoplásicos/farmacologia , Separação Celular , Resistencia a Medicamentos Antineoplásicos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Neoplasias/tratamento farmacológico , Células-Tronco Neoplásicas/efeitos dos fármacos
18.
Oncol Lett ; 14(6): 7715-7722, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29250173

RESUMO

Metastasis is the major cause of triple-negative breast cancer (TNBC)-associated mortality. Hypoxia promotes cancer cell migration and remote metastasis, which occur with hypoxia inducible factor 1α (HIF-1α) stabilization and vimentin upregulation. However, the evolutionary dynamics that link the changes in HIF-1α and vimentin levels under hypoxic conditions are not well understood. In the present study, the effects of intermittent hypoxia (IH), continuous hypoxia (CH) and normoxia on the migration and proliferation of human TNBC MDA-MB-231 cells were investigated. The results demonstrated that IH significantly increased the migration of MDA-MB-231 cells, and this effect was dependent on the number of cycles of hypoxia-reoxygenation. Unexpectedly, IH significantly inhibited cell proliferation, while CH only caused such an effect if hypoxia extended for ≥3 days. IH and CH induced HIF-1α protein accumulation and vimentin upregulation, with a greater effect observed in IH. Knockdown of HIF-1α with siRNA abolished IH-induced cell migration and vimentin upregulation. In summary, multiple cycles of hypoxia and reoxygenation have a more pronounced effect on the promotion of TNBC invasiveness than CH; HIF-1α activation and downstream vimentin upregulation may account for this phenotypic change.

19.
Sensors (Basel) ; 17(12)2017 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-29189753

RESUMO

In this paper, we present a stable silver-based surface plasmon resonance (SPR) sensor using a self-assembled monolayer (SAM) as a protection layer and investigated its efficiency in water and 0.01 M phosphate buffered saline (PBS). By simulation, silver-based SPR sensor has a better performance in field enhancement and penetration depth than that of a gold-based SPR sensor, which are 5 and 1.4 times, respectively. To overcome the instability of the bare silver film and investigate the efficiency of the protected layer, the SAM of 11-mercapto-1-undecanol (MUD) was used as a protection layer. Stability experiment results show that the protected silver film exhibited excellent stability either in pure water or 0.01 M PBS buffer. The sensitivity of the silver-based SPR sensor was calculated to be 127.26 deg/RIU (refractive index unit), measured with different concentrations of NaCl solutions. Further, a very high refractive resolution for the silver-based SPR sensor was found to be 2.207 × 10-7 RIU, which reaches the theoretical limit in the wavelength of 632.8 nm for a SPR sensor reported in the literature. Using a mixed SAM of 16-mercaptohexadecanoic acid (MHDA) and a MUD layer with a ratio of 1:10, this immunosensor for the rabbit immunoglobulin G (IgG) molecule with a limit of detection as low as 22.516 ng/mL was achieved.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA