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1.
World Neurosurg ; 136: e559-e566, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31958591

RESUMO

BACKGROUND: Microvascular decompression (MVD) has been the most effective long-term surgical treatment of trigeminal neuralgia (TN). However, the risk factors for poor pain control after MVD are not fully understood. METHODS: A total of 184 patients with typical TN who had undergone MVD at our institution from January 3, 2008 to January 3, 2016 were enrolled in the present study. The data were collected from the electronic operative records and case notes and retrospectively analyzed. Patients were followed up at the outpatient department or by telephone at a minimum of 3 months and a maximum of 48 months postoperatively. RESULTS: Of the 184 patients enrolled in the present study, 72.3% had had freedom from pain after MVD and 27.7% had experienced poor pain control at the follow-up examinations (minimum, 3 months; maximum, 48 months). The risk factors for poor pain control after MVD using binary logistic regression and receiver operating characteristic curve analysis included younger age (odds ratio [OR], 0.90; 95% confidence interval [CI], 0.82-0.99; P = 0.028; area under the curve [AUC], 0.774), poor preoperative pain control (Barrow Neurological Institute score >IV; OR, 52.03; 95% CI, 6.44-420.16; P < 0.001; AUC, 0.858), intraoperatively detected multivessel compression (OR, 2.49; 95% CI, 3.10-46.59, P < 0.001; AUC, 0.871). Furthermore, combined compression of the superior cerebellar artery and petrosal vein was an independent risk factor predicting a poor outcome after MVD (OR, 5.69; 95% CI, 33.78-2579.03; P < 0.001; AUC, 0.812). CONCLUSIONS: Younger patients with TN had worse long-term pain outcomes after MVD. The additional factors associated with postoperative recurrence included poor preoperative pain control (Barrow Neurological Institute score >IV) and multivessel compression. Furthermore, combined compression of the superior cerebellar artery and petrosal vein was associated with worse outcomes.


Assuntos
Cirurgia de Descompressão Microvascular , Neuralgia do Trigêmeo/cirurgia , Fatores Etários , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Resultado do Tratamento
2.
Cell Transplant ; 28(8): 1025-1032, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31129993

RESUMO

Intracerebral hemorrhage (ICH) is one of the most devastating forms of cerebrovascular pathology. However, its treatment remains a matter of debate among neurosurgeons and neurologists. The study was to explore the efficacy of minimally invasive surgery (stereotactic catheter drainage, SCD) for patients with severe intracerebral hemorrhage (Glasgow Coma Scale, GCS) score ≤ 8 and hematoma volume ≥ 30 cm3) and to determine predisposing factors for good clinical outcome. A total of 75 patients with severe ICH were included in this retrospective study. Patients were assigned to the SCD group (n=38) or the conventional craniotomy group (n=37). Patients were followed up for 12 months postoperatively, and their clinical parameters were compared. During the operation, the SCD group exhibited a lower bleeding volume (p<0.001) and shorter operating time (p<0.001) than the conventional craniotomy group. For postoperative efficacy, the rates of pneumonia and tracheotomy were lower (p=0.002 and p=0.027, respectively), and the duration of hospital and neurosurgery intensive care unit (NSICU) in days were significantly shorter in the SCD group (p=0.046 and p=0.047, respectively). Furthermore, patients in the SCD group showed improved modified Rankin Scale (mRS) scores at discharge (p<0.018) and at 12-month follow up (p<0.001). Predisposing factors for good clinical outcomes were hematoma volume (<50 cm3, 95% confidence interval (CI): 1.043-1.956, p<0.046), initial GCS score (>6, 95% CI: 3.248-187.466, p<0.001), hypertension (none, 95% CI: 1.440-2.922, p<0.001), and treatment modality (SCD, 95% CI: 1.422-3.226, p<0.001). Taken together, SCD surgery is safe and effective in patients with severe ICH and has fewer complications and better clinical outcomes than conventional craniotomy.

3.
Sci Total Environ ; 646: 716-726, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30059931

RESUMO

The combustion behaviors of anthracite and dried sawmill sludge (DSS) were studied using thermogravimetric analysis (TGA) and derivative thermogravimetric analysis (DTG). DSS was found to be a promoter for anthracite combustion, the addition of DSS in anthracite decreased the burnout temperature and time. But DSS caused the rapid releases of SO2 and NO in the initial combustion stage. In overall, the increasing of DSS significantly decreased the emission factor of SO2 from 13.42 ±â€¯1.80 to 0.31 ±â€¯0.08 g/kg; while the emission factor of NO was not obviously changed and stable at 0.7-0.8 g/kg in all cases. The oxygen-rich atmosphere was helpful for the rapid and sufficient combustion of blend; the oxygen-lean atmosphere delayed the combustion process and slowed down the releases of SO2 and NO. The increasing combustion temperature improved the anthracite combustion, and the emission factors of SO2 and NO were all increased with the temperature increasing. 900 °C was found to be the best combustion temperature for NO generation. SO3 was detected in the combustion of anthracite under 21% and 30% of O2. Two promising ways for control of SO2 and NO were provided: 1) urea-fuel mixture combustion combined with the post-combustion wet absorption by Na2CO3; 2) post-combustion wet absorption by NaClO/Na2CO3. The removal efficiencies of SO2 and NO could reach 100% and over 95% respectively. The removal products were determined as sulfate, sulfite and nitrate by IC, with no toxic byproducts being produced.

4.
World Neurosurg ; 118: e115-e122, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29959072

RESUMO

OBJECTIVE: To investigate the clinical efficacy of navigation-guided minimally invasive surgery in patients with hypertensive basal ganglia hemorrhage. METHODS: A total of 64 patients with hypertensive basal ganglia hemorrhage were enrolled in this retrospective study. They were divided into a navigation group and a traditional group based on surgical approaches. The data for the 2 groups of patients were analyzed with regard for the hematoma clearance rate, duration of surgery, duration of hospitalization, Glasgow Outcome Scale score at discharge, Barthel index score at 6 months, and postoperative complication rates for rebleeding and pneumonia. RESULTS: There were no significant differences in basic characteristics between the 2 groups (P > 0.05). The hematoma clearance rate was significantly lower in the navigation group (49.18 ± 16.76%) than in the traditional group (84.29 ± 6.91%, P < 0.01). The duration of surgery and duration of hospitalization were significantly shorter in the navigation group (55.00 ± 11.89 minutes and 24.25 ± 7.1 days, respectively) than in the traditional group (156.38 ± 47.9 minutes and 32.63 ± 9.8 days, respectively; both P < 0.01). There were also significant differences between the 2 groups in Glasgow Outcome Scale scores (P = 0.006). The Barthel index scores were significantly greater in the navigation group (73.13 ± 18.76) than in the traditional group (57.63 ± 26.63, P < 0.05). There were no significant differences between the 2 groups in the complication rates (P > 0.05). CONCLUSIONS: Under certain conditions, compared with standard craniotomy and hematoma evacuation, navigation-guided hematoma puncture aspiration and catheter drainage is simple, effective, and safe as a treatment for hypertensive basal ganglia hemorrhage.


Assuntos
Hemorragia dos Gânglios da Base/cirurgia , Drenagem/métodos , Hematoma/cirurgia , Hipertensão/cirurgia , Terapia de Campo Magnético/métodos , Neuronavegação/métodos , Adulto , Idoso , Hemorragia dos Gânglios da Base/diagnóstico por imagem , Craniotomia/métodos , Feminino , Hematoma/diagnóstico por imagem , Humanos , Hipertensão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Estudos Retrospectivos , Resultado do Tratamento
5.
BMC Surg ; 17(1): 123, 2017 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-29202748

RESUMO

BACKGROUND: Delayed epidural hematoma (DEH) following evacuation of traumatic acute subdural hematoma (ASDH) or acute epidural hematoma (EDH) is a rare but devastating complication, especially when it occurs sequentially in a single patient. CASE PRESENTATION: A 19-year-old man who developed contralateral DEH following craniotomy for evacuation of a traumatic right-side ASDH and then developed a left-side DEH of the posterior cranial fossa after craniotomy for evacuation of the contralateral DEH. He was immediately returned to the operating room for additional surgeries and his neurological outcome was satisfactory. CONCLUSIONS: Although DEH occurring after evacuation of ASDH or acute EDH is a rare event, timely recognition is critical to prognosis.


Assuntos
Craniectomia Descompressiva/métodos , Hematoma Epidural Craniano/etiologia , Hematoma Subdural Agudo/cirurgia , Humanos , Masculino , Complicações Pós-Operatórias/etiologia , Prognóstico , Adulto Jovem
6.
Oncotarget ; 8(33): 55435-55442, 2017 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-28903431

RESUMO

To explore the relationship between certain pathogens, such as chlamydia pneumonia (Cpn) and cytomegalovirus (CMV), and carotid atherosclerosis (AS) in a Chinese population.Twenty-five carotid atherosclerotic stenosis patients from the Beijing Tiantan Hospital (affiliated with Capital Medical University) participated in the study. After undergoing digital subtraction angiography (DSA) and/or computed tomography angiography (CTA), the degree of carotid artery stenosis was over 70% in all cases, and the patients underwent carotid endarterectomy. Plaque specimens were obtained during surgery. The streptavidin-peroxidase (SP) method was used to test the Cpn and CMV antigens in the specimens, and the relationship between the Cpn and CMV pathogen infections and AS was analyzed based on the test results. In the group of 25 carotid atherosclerotic specimens, the detection rate of the Cpn-specific antigens was 84.0% (21/25). In the control group, the detection rate was 13.3% (2/15) in the ascending aortic intima. Thus, the between-group difference was significant (P<0.01). The CMV-specific antigen detection rate was 72.0% (18/25) using the same experimental group specimens, and the detection rate was zero in the control group. Thus, there were significant between-group differences (P<0.01). Due to the high detection rate of Cpn- and CMV-specific antigens in carotid atherosclerotic plaque in a Chinese population, it can be inferred that pathogens such as Cpn and CMV are one factor associated with carotid atherosclerosis.

7.
Oncotarget ; 8(16): 27582-27592, 2017 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-28187439

RESUMO

Glioma is regarded as the most prevalent malignant carcinoma of the central nervous system. Thus, the development of new therapeutic strategies targeting glioma is of significant clinical importance. Long non-coding RNAs (lncRNAs) are functional RNA molecules without a protein-coding function and are reportedly involved in the initiation and progression of glioma. Dysregulation of lncRNAs in glioma is due to activation of several signaling pathways, such as the BRD4-HOTAIR-ß-catenin/PDCD4, p53-Hif-H19/IGF2 and CRNDE/mTOR pathways. Furthermore, microRNAs (miRNAs) such as miR-675 also interact with lncRNAs in glioma. Thus, exploring the mechanisms by which lncRNA control processes will be instrumental for devising new effective therapies against glioma.


Assuntos
Regulação Neoplásica da Expressão Gênica , Glioma/genética , RNA Longo não Codificante/genética , Animais , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Modelos Animais de Doenças , Metabolismo Energético , Redes Reguladoras de Genes , Glioma/metabolismo , Glioma/patologia , Humanos , MicroRNAs/genética , Interferência de RNA , Transdução de Sinais , Microambiente Tumoral/genética
8.
BMC Surg ; 17(1): 3, 2017 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-28068964

RESUMO

BACKGROUND: Penetrating brain injury (PBI) can be caused by several objects ranging from knives to chopsticks. However, an assault with long and electric screwdriver is a peculiar accident and is relatively rare. Because of its rarity, the treatments of such injury are complex and nonstandardized. CASE PRESENTATION: We presented a case of a 54-year-old female who was stabbed with a screwdriver in her head and accompanied by loss of consciousness for 1 h. Computer tomography (CT) demonstrated that the screwdriver passed through the right zygomatic bone to posterior cranial fossa. Early foreign body removal and hematoma evacuation were performed and the patient had a good postoperative recovery. CONCLUSIONS: In this study, we discussed the clinical presentation and successful management of such a unique injury caused by a screwdriver. Our goal is to demonstrate certain general management principles which can improve patient outcomes.


Assuntos
Hemorragia Encefálica Traumática/cirurgia , Traumatismos Cranianos Penetrantes/cirurgia , Hemorragia Subaracnoídea Traumática/cirurgia , Hemorragia Encefálica Traumática/diagnóstico por imagem , Fossa Craniana Posterior/lesões , Feminino , Traumatismos Cranianos Penetrantes/diagnóstico por imagem , Humanos , Pessoa de Meia-Idade , Hemorragia Subaracnoídea Traumática/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Zigoma/lesões
9.
Oncotarget ; 7(43): 71052-71061, 2016 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-27626493

RESUMO

Hyperglycemia after severe traumatic brain injury (TBI) occurs frequently and is associated with poor clinical outcome and increased mortality. In this review, we highlight the mechanisms that lead to hyperglycemia and discuss how they may contribute to poor outcomes in patients with severe TBI. Moreover, we systematically review the proper management of hyperglycemia after TBI, covering topics such as nutritional support, glucose control, moderated hypothermia, naloxone, and mannitol treatment. However, to date, an optimal and safe glycemic target range has not been determined, and may not be safe to implement among TBI patients. Therefore, there is a mandate to explore a reasonable glycemic target range that can facilitate recovery after severe TBI.


Assuntos
Lesões Encefálicas Traumáticas/complicações , Encéfalo/metabolismo , Glucose/metabolismo , Hiperglicemia/terapia , Hipoglicemiantes/uso terapêutico , Glicemia/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Lesões Encefálicas Traumáticas/sangue , Lesões Encefálicas Traumáticas/mortalidade , Lesões Encefálicas Traumáticas/terapia , Diuréticos Osmóticos/uso terapêutico , Humanos , Hiperglicemia/sangue , Hiperglicemia/etiologia , Hiperglicemia/mortalidade , Hipotermia Induzida , Insulina/uso terapêutico , Hipertensão Intracraniana/tratamento farmacológico , Hipertensão Intracraniana/etiologia , Manitol/uso terapêutico , Naloxona/uso terapêutico , Fatores de Risco
10.
Mol Med Rep ; 10(1): 423-8, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24789576

RESUMO

AP-2 transcription factors are important sequence-specific DNA-binding regulators that are expressed in the neural crest and other tissues during mammalian development. The human AP-2 family of transcription factors consists of five members, AP-2α, -ß, -γ, -δ and -ε, which have an important role in the regulation of gene expression during development and in the differentiation of multiple organs and tissues. The present study aimed to investigate the mechanism by which AP-2δ mediates heme oxygenase-1 (HMOX1) gene expression. It was identified that the human AP-2δ protein exhibited weak binding to a suboptimal AP-2 sequence, 5'-GCCN3GGC-3', to which all other AP-2 proteins bind in vitro, providing the first example of DNA target specificity amongst the AP-2 family. AP-2δ protein bound to an optimized AP-2 consensus DNA sequence, 5'-GCCTGAGGC-3', in vitro and transactivated gene expression in eukaryotic cells. The transactivation domain of Ap-2δ differs notably from those in the other AP-2 proteins as it lacks the PY motif (XPPXY) and several other conserved residues that are important for the transcriptional activity of AP-2 proteins, yet it functions as an equally strong activator.


Assuntos
DNA/metabolismo , Heme Oxigenase-1/metabolismo , Fator de Transcrição AP-2/metabolismo , Motivos de Aminoácidos , Animais , Sequência de Bases , Sítios de Ligação , Linhagem Celular , Clonagem Molecular , Heme Oxigenase-1/genética , Humanos , Camundongos , Células NIH 3T3 , Regiões Promotoras Genéticas , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Fator de Transcrição AP-2/genética , Ativação Transcricional
11.
J Biosci Bioeng ; 115(2): 133-7, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23010750

RESUMO

A thermostable GDSL family esterase-encoding gene, EstL5, was directly obtained from the genomic DNA of Geobacillus thermodenitrificans T2. Recombinant hexahistidine-tagged EstL5 was overexpressed, purified, and its biochemical properties were partially characterized. EstL5 was observed to be active within the temperature range of 0-80°C, having maximal activity at 60°C. Unlike most other thermostable enzymes, EstL5 displayed 24% of its highest activity at 0°C. EstL5 exhibited a high level of activity within a pH range of 6.0-11.0, showing the highest activity at pH 8.0. EstL5 also retained 100% of its activity after a 12-h incubation at 55°C. Furthermore, this enzyme was observed to be strongly inhibited by 10% (w/v) SDS and 0.1 mM PMSF.


Assuntos
Esterases/química , Esterases/metabolismo , Geobacillus/enzimologia , Motivos de Aminoácidos , Sequência de Aminoácidos , Clonagem Molecular , Estabilidade Enzimática , Esterases/antagonistas & inibidores , Esterases/genética , Esterases/isolamento & purificação , Geobacillus/genética , Concentração de Íons de Hidrogênio , Indicadores e Reagentes/farmacologia , Modelos Moleculares , Dados de Sequência Molecular , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética , Proteínas Recombinantes/isolamento & purificação , Temperatura
12.
Curr Alzheimer Res ; 10(1): 63-71, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22272609

RESUMO

Association studies between Alpha-1-antichymotrypsin (ACT)-17(A > T) polymorphisms and Alzheimer's disease (AD) susceptibility have shown conflicting results. In this investigation, we performed a meta-analysis to assess the purported associations. Subgroup analyses based on ethnicity (Caucasians, East-Asian and American mixed) were also performed including a total of 5,676 AD patients and 5,460 controls for ACT-17. Overall, allele contrast (A vs. T) of ACT -17 polymorphism produced significant results in the worldwide population [P(heterogeneity)=0.01, random-effects (RE) odds ratio (OR) 1.12; 95% CI 1.04-1.21, P=0.003] and in the Caucasian population [P(heterogeneity)=0.03, RE OR1.11 95% CI 1.01-1.24, P=0.04]. Meta-analyses of other genetic contrasts suggested that the A allele carriers are associated with increased susceptibility to AD in variant populations. No significant association was observed in the East-Asian subgroup analysis. In conclusion, ACT-17 variation presents a risk factor for AD in the worldwide population, especially in the Caucasian population.


Assuntos
Doença de Alzheimer/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , alfa 1-Antiquimotripsina/genética , Feminino , Frequência do Gene , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Estudos Retrospectivos , Sensibilidade e Especificidade
13.
Protein J ; 31(4): 275-84, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22418839

RESUMO

Human ankyrin repeat and suppressor of cytokine signaling box protein 9 (hASB9) is a specific substrate-recognition subunit of an elongin C-cullin-SOCS box E3 ubiquitin ligase complex. It recognizes its substrate, brain type creatine kinase (CKB), using the ankyrin repeat domain; and facilitates the polyubiquitination of CKB to mediate proteasomal degradation through the SOCS box domain. HASB9-2 is an isoform of hASB9 that contains one ankyrin repeat domain. In this study, the crystal structure of hASB9-2 is shown at 2.2-Å resolution using molecular replacement. Overall, hASB9-2 forms a slightly curved arch with a characteristic L-shaped cross-section. Amino acid substitution analysis based on docking experiments revealed that His103 and Phe107 in hASB9-2 are essential for binding to CKB. Analysis of truncation mutants demonstrated that the first six ankyrin repeats along with the N-terminal region of hASB9-2 contribute to the interaction with CKB.


Assuntos
Creatina Quinase Forma BB/metabolismo , Proteínas Supressoras da Sinalização de Citocina/química , Proteínas Supressoras da Sinalização de Citocina/metabolismo , Sequência de Aminoácidos , Repetição de Anquirina , Sítios de Ligação , Creatina Quinase Forma BB/química , Creatina Quinase Forma BB/genética , Cristalografia por Raios X , Humanos , Cinética , Modelos Moleculares , Dados de Sequência Molecular , Ligação Proteica , Alinhamento de Sequência , Especificidade por Substrato , Proteínas Supressoras da Sinalização de Citocina/genética
14.
Mol Biol Rep ; 38(4): 2771-83, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21104141

RESUMO

LNX protein is the first described PDZ domain-containing member of the RING finger-type E3 ubiquitin ligase family. Studies have approved that LNX could participate in signal transduction, such as Notch pathway, and play an important role in tumorigenesis. In this study, we found that down-regulation of LNX resulted in G0/G1 cell cycle arrest in G0/G1 phase in HEK293 cells. To explore the molecular mechanism of this phenomenon, we employed expression microarray to comparatively analyze the genome-wide expression between the LNX-knockdown cells and the normal cells. We also used quantitative real-time PCR to further confirm the differential expression patterns of 25 transcripts involved in cell cycle. Combined with known information about genic functions, signal pathways and cell cycle machinery, we analyzed the role of endogenous LNX in cell cycle. The results suggest that down-regulation of LNX could result in cell cycle arrest in G0/G1 phase through inhibition of ß-catenin, MAPK, NFκB, c-Myc-dependent pathway and activation of p53, TGF-ß-dependent pathway. This study provides new perspectives on LNX's pleiotropic activities, especially its essential role in cell proliferation and cell cycle.


Assuntos
Ciclo Celular/fisiologia , Regulação da Expressão Gênica/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais/genética , Ubiquitina-Proteína Ligases/genética , Linhagem Celular , Primers do DNA/genética , Perfilação da Expressão Gênica , Técnicas de Silenciamento de Genes , Vetores Genéticos/genética , Humanos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Oligonucleotídeos/genética , RNA Interferente Pequeno/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Crescimento Transformador beta/metabolismo , Proteína Supressora de Tumor p53/metabolismo , beta Catenina/metabolismo
15.
Acta Pharmacol Sin ; 31(11): 1487-94, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21052085

RESUMO

AIM: To construct a system for selecting reference genes (RGs) and to select the most optimal RGs for gene expression studies in nasopharyngeal carcinoma (NPC). METHODS: The total RNAs from 20 NPC samples were each labeled with Cy5-dUTP. To create a common control, the total RNA from 15 nasopharyngeal phlogistic (NP) tissues was mixed and labeled via reverse transcription with Cy3-dUTP. cDNA microarrays containing 14 112 genes were then performed. A mathematical approach was constructed to screen stably expressed genes from the microarray data. Using this method, three genes (YARS, EIF3S7, and PFDN1) were selected as candidate RGs. Furthermore, 7 commonly used RGs (HPRT1, GAPDH, TBP, ACTB, B2M, G6PDH, and HBB) were selected as additional potential RGs. Real-time PCR was used to detect these 10 candidate genes' expression levels and the geNorm program was used to find the optimal RGs for NPC studies. RESULTS: On the basis of the 10 candidate genes' expression stability level, geNorm analysis identified the optimal single RG (YARS or HPRT1) and the most suitable set of RGs (HPRT1, YARS, and EIF3S7) for NPC gene expression studies. In addition, this analysis determined that B2M, G6PDH, and HBB were not appropriate for use as RGs. Interestingly, ACTB was the least stable RG in our study, even though previous studies had indicated that it was one of the most stable RGs. Three novel candidate genes (YARS, EIF3S7, and PFDN1), which were selected from microarray data, were all identified as suitable RGs for NPC research. A RG-selecting system was then constructed, which combines microarray data analysis, a literature screen, real-time PCR, and bioinformatic analysis. CONCLUSION: We construct a RG-selecting system that helps find the optimal RGs. This process, applied to NPC research, determined the single RG (YARS or HPRT1) and the set of RGs (HPRT1, YARS, and EIF3S7) that are the most suitable internal controls.


Assuntos
Perfilação da Expressão Gênica/métodos , Expressão Gênica , Neoplasias Nasofaríngeas/genética , Carcinoma , Regulação Neoplásica da Expressão Gênica , Humanos , Carcinoma Nasofaríngeo , Análise de Sequência com Séries de Oligonucleotídeos , RNA/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa
16.
J Pharmacol Exp Ther ; 334(3): 847-53, 2010 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-20551295

RESUMO

Hypericin-mediated photodynamic therapy (HY-PDT) has become a potential treatment for tumors and nonmalignant disorders. Some studies reported that HY-PDT could lead to apoptosis in some carcinoma cells. However, the molecular mechanism of HY-PDT remains unknown. In this study, we evaluated the molecular mechanisms of hypericin associated with light-emitting diode irradiation on the poorly differentiated human nasopharyngeal carcinoma cell line CNE-2 in vitro. To comprehensively understand the effects of HY-PDT on CNE-2 cells, we detected cell viability, cell cycle, apoptosis, intracellular glutathione content, and intracellular caspase (caspase-9, caspase-3, and caspase-8) activity. Furthermore, we performed genome-wide expression analysis via microarrays at different time points in response to HY-PDT, and we found that differentially expressed genes were highly enriched in the pathways related to reactive oxygen species generation, mitochondrial activity, DNA replication and repair, cell cycle/proliferation, and apoptosis. These results were consistent with our cytology test results and demonstrated that caspase-dependent apoptosis occurred after HY-PDT. Taken together, both cellular and molecular data revealed that HY-PDT could inhibit the growth of CNE-2 cells and induce their apoptosis.


Assuntos
Neoplasias Nasofaríngeas/tratamento farmacológico , Perileno/análogos & derivados , Fotoquimioterapia/métodos , Radiossensibilizantes/uso terapêutico , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Caspases/metabolismo , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/efeitos da radiação , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Reparo do DNA , Replicação do DNA/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Estudo de Associação Genômica Ampla , Glutationa/metabolismo , Humanos , Luz , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Perileno/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo
17.
Front Biosci (Elite Ed) ; 2: 829-40, 2010 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-20515756

RESUMO

The purpose of this study was to identify and validate novel prognostic biomarkers in human hepatocellular carcinoma (HCC). We analyzed gene expression profiles not only between 33 HCCs and their corresponding noncancerous liver tissues, but also between 25 HCCs and pooled normal liver tissues using cDNA microarrays containing 12800 genes. Functional analysis of differentially expressed genes involved in HCC carcinogenesis and tumor progression revealed that up-regulated and down-regulated genes are mainly associated with cell cycle and immune response, respectively. We detected two regions of cytogenetic changes only in poorly-differentiated HCCs using the expression data. We identified a 9-gene expression signature, which was able to predict differentiation degree and survival of HCC samples. Among the 9 most discriminatory genes, minichromosome maintenance protein 2 (MCM2), a significantly up-regulated gene involved in cell cycle pathway, was selected for further analysis. Overexpression of MCM2 protein related to poor-differentiation in HCC was validated using tissue microarray-based immunohistochemistry containing 96 HCCs. Our studies show that the 9-gene expression signature may serve as promising prognostic biomarkers involved in hepatocarcinogenesis and tumor progression.


Assuntos
Biomarcadores/metabolismo , Carcinoma Hepatocelular/genética , Perfilação da Expressão Gênica , Neoplasias Hepáticas/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Diferenciação Celular , Aberrações Cromossômicas , DNA Complementar , Humanos , Imuno-Histoquímica , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Análise de Sequência com Séries de Oligonucleotídeos , Prognóstico
18.
Front Biosci (Schol Ed) ; 2: 1127-44, 2010 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-20515845

RESUMO

To investigate genetic mechanisms of hepatocarcinogenesis and identify potential anticancer targets in hepatocellular carcinoma (HCC), we analyzed microarray gene expression profiles between 33 HCCs and their corresponding noncancerous liver tissues. Functional analysis of differentially-expressed genes in HCC indicated that cell cycle dysregulation plays an important role in hepatocarcinogenesis. Based on 14 differentially-expressed genes involved in cell cycle in HCC, we applied Structural Equation Modeling (SEM) to establish a potential genetic network which could assist understanding of HCC molecular mechanisms. siRNA-mediated knock-down of two significantly up-regulated genes, minichromosome maintenance protein 2 (MCM2) and cyclin B1 (CCNB1), in HCC cells (SMMC-7721 and QGY-7703) induced G2/M-phase arrest, apoptosis and antiproliferation in HCC. Some up-regulated cell cycle-related genes in HCC were down-regulated following specific depletion of MCM2 or/and CCNB1 in HCC cells, which might well validate and complement the reconstructed cell cycle network. This study may contribute to further disclose hepatocarcinogenesis mechanism through systematically analyzed the HCC-related-cell-cycle pathway. This study also shows that MCM2 and CCNB1 could be promising prognostic and therapeutic targets for HCC.


Assuntos
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Ciclo Celular/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Apoptose/genética , Sequência de Bases , Proteínas de Ciclo Celular/antagonistas & inibidores , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Ciclina B1/antagonistas & inibidores , Ciclina B1/genética , Expressão Gênica , Redes Reguladoras de Genes , Humanos , Componente 2 do Complexo de Manutenção de Minicromossomo , Modelos Genéticos , Proteínas Nucleares/antagonistas & inibidores , Proteínas Nucleares/genética , Interferência de RNA , RNA Interferente Pequeno/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Biologia de Sistemas
19.
Mol Biol Rep ; 37(7): 3547-52, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20174874

RESUMO

Bim is a proapoptotic member of the Bcl-2 family and is primarily involved in the regulation of the intrinsic apoptotic pathway. However, the detail of regulation of Bim's proapoptotic activity has not been clarified yet. Using Bim L as bait, we screened a human fetal cDNA library for interacting proteins and identified Grb10 as an interactor. This interaction was verified by co-immunoprecipitation and intracellular co-localization studies. The potential segment of Bim L that binds Grb10 was identified via a yeast mating test. Grb10 interacted with the DBD (dynein binding domain) of Bim and inhibited apoptosis triggered by overexpression of DBD containing Bim isoforms. The putative phosphorylation sites on DBD of Bim play a role for the anti-proapoptotic activity of Grb10. Our results suggest that Grb10 interacts with Bim L and inhibits its proapoptotic activity in a phosphorylation-dependant manner.


Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Apoptose , Proteína Adaptadora GRB10/metabolismo , Proteínas de Membrana/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Proteína 11 Semelhante a Bcl-2 , Células HEK293 , Humanos , Imunoprecipitação , Espaço Intracelular/metabolismo , Ligação Proteica , Isoformas de Proteínas/metabolismo , Transporte Proteico , Proteínas Recombinantes de Fusão/metabolismo , Saccharomyces cerevisiae/metabolismo , Frações Subcelulares/metabolismo , Técnicas do Sistema de Duplo-Híbrido
20.
J Control Release ; 144(1): 46-54, 2010 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-20093155

RESUMO

Trimethyl chitosan-cysteine conjugate (TMC-Cys) was evaluated as non-viral gene carriers to combine the advantages of TMC and thiolated chitosan. TMC-Cys with various molecular weights (30, 100, and 200 kDa) and quaternization degrees (15 and 30%) was allowed to form polyelectrolyte nanocomplexes with plasmid encoding enhanced green fluorescence protein (pEGFP), which demonstrated preferable diameters of below 200 nm and zeta potentials of +15 to +20 mV. Cell binding and uptake of TMC-Cys/pEGFP nanocomplexes (TMC-Cys NC) were enhanced 2.4-3.0 and 1.4-3.0 folds, respectively, compared to TMC/pEGFP nanocomplexes (TMC NC). pEGFP could be easily released from TMC-Cys NC at the intracellular glutathione concentration, which promoted its nuclear transport and accumulation. Consequently, TMC-Cys NC showed a 1.4 to 3.2-fold increase in the transfection efficiency in HEK293 cells as compared to TMC NC and the optimal TMC-Cys(100,30) NC showed a 1.5-fold enhancement than Lipofectamine2000. Such results were further confirmed by in vivo transfection with a 2.3-fold and 4.1-fold higher transfection efficiency of TMC-Cys(100,30) NC than TMC(100,30) NC and Lipofectamine2000, respectively. Therefore, TMC-Cys/DNA nanocomplexes could be a promising gene delivery system with in vitro and in vivo superiority to Lipofectamine2000.


Assuntos
Quitosana/química , Transfecção/métodos , Transporte Biológico , Transporte Biológico Ativo , DNA , Técnicas de Transferência de Genes , Genes , Proteínas de Fluorescência Verde , Humanos , Peso Molecular , Plasmídeos
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