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1.
Chin Med J (Engl) ; 133(12): 1404-1408, 2020 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-32472784

RESUMO

BACKGROUND: It is a challenge to characterize the consciousness level of patients with severe disturbance of consciousness and predict their prognosis effectively for Chinese doctors. We aimed to investigate the psychometric property and the diagnostic practicality of severe disturbance of consciousness by Chinese Nanjing persistent vegetative state scale (CNPVSS) which was first set up in 1996 and modified in 2001 and 2011. METHODS: The concurrent validity, inter-rater consistency and diagnostic accuracy of CNPVSS and Chinese version of coma recovery scale-revised (CRS-R) were investigated by assessment of 380 patients with severe disorders of consciousness. RESULTS: Total scores of the CNPVSS were correlated significantly with that of the CRS-R, indicating acceptable concurrent validity. Sub-scale analysis showed moderate to high inter-rater reliability and test-retest reliability. CNPVSS was superior to CRS-R on the diagnosis sensitivity. The CNPVSS was able to distinguish 65 patients in emergence from minimal consciousness state who were misclassified as in minimal consciousness state (MCS) by the CRS-R, and it could also distinguish two patients in MCS who were misclassified as in vegetative state by the CRS-R. CONCLUSION: The CNPVSS is an appropriate measurement and is sensitive to distinguish the MCS patients from the VS patients.

2.
Chem Biodivers ; 17(5): e2000103, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32180346

RESUMO

Three dimeric cassane diterpenoids, caesalpanins A-C, were isolated from the seeds of Caesalpinia sappan L., as well as three known compounds. Their structures were determined via analysis of 1D-, 2D-NMR, and HR-ESI-MS data. Caesalpanins A and B were the second and third compounds that presented a nitrogen-containing cassane diterpenoid dimer linked through one ether bond between C-19 and C-20'. Caesalpanin B exhibited moderate cytotoxic activity against MCF-7 cell lines with IC50 value of 29.98 µm. Caesalpanins A and B had weak inhibitory effects against LPS-induced nitric oxide (NO) production in RAW 264.7 macrophages at 50 µm with inhibitory rate of 36.01 % and 32.93 %, respectively.

3.
Chem Biodivers ; 16(5): e1900013, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30811806

RESUMO

Thirteen sesquiterpenes including eight new ones, magnodelavins A-H (1-8), were obtained from the 95 % ethanolic extract of the leaves of Magnolia delavayi Franch. The structures of the new compounds were determined by exhaustive 1 H-, 13 C-, 2D-NMR, UV, IR, and HR-ESI-MS data, as well as X-ray crystallographic analysis. Compounds 9 and 10 showed potent cytotoxic activities against HL-60, A-549, SMMC-7721, MCF-7, and SW480 human cancer cell lines in vitro using MTS assay.


Assuntos
Antineoplásicos Fitogênicos/química , Magnolia/química , Sesquiterpenos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cristalografia por Raios X , Ensaios de Seleção de Medicamentos Antitumorais , Células HL-60 , Humanos , Espectroscopia de Ressonância Magnética , Magnolia/metabolismo , Conformação Molecular , Folhas de Planta/química , Folhas de Planta/metabolismo , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacologia , Espectrometria de Massas por Ionização por Electrospray
4.
Neural Regen Res ; 13(11): 1919-1926, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30233065

RESUMO

Long non-coding RNAs regulate brain microvascular endothelial cell death, the inflammatory response and angiogenesis during and after ischemia/reperfusion and oxygen-glucose deprivation/reoxygenation (OGD/R) insults. The long non-coding RNA, SNHG12, is upregulated after ischemia/reperfusion and OGD/R in microvascular endothelial cells of the mouse brain. However, its role in ischemic stroke has not been studied. We hypothesized that SNHG12 positively regulates ischemic stroke, and therefore we investigated its mechanism of action. We established an OGD/R mouse cell model to mimic ischemic stroke by exposing brain microvascular endothelial cells to OGD for 0, 2, 4, 8, 16 or 24 hours and reoxygenation for 4 hours. Quantitative real-time polymerase chain reaction showed that SNHG12 levels in brain microvascular endothelial cells increased with respect to OGD exposure time. Brain microvascular endothelial cells were transfected with pcDNA-control, pcDNA-SNHG12, si-control, or si-SNHG12. After exposure to OGD for 16 hours, these cells were then analyzed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, trypan blue exclusion, western blot, and capillary-like tube formation assays. Overexpression of SNHG12 inhibited brain microvascular endothelial cell death and the inflammatory response but promoted angiogenesis after OGD/R, while SNHG12 knockdown had the opposite effects. miR-199a was identified as a target of SNHG12, and SNHG12 overexpression reversed the effect of miR-199a on brain microvascular endothelial cell death, the inflammatory response, and angiogenesis. These findings suggest that SNHG12 suppresses endothelial cell injury induced by OGD/R by targeting miR-199a.

5.
Artigo em Inglês | MEDLINE | ID: mdl-29808625

RESUMO

INTRODUCTION: The clinical target volume (CTV) delineation is crucial for tumour control and normal tissue protection. This study investigated the contralateral extension of nasopharyngeal carcinoma (NPC) in patients with a clinically diagnosed unilateral tumour to pursue the possibility of CTV reduction. METHODS: Twenty NPC patients with localized tumours confined to only one side of the nasopharynx as shown by magnetic resonance imaging and fibreoptic endoscopy were selected for biopsy. The tissues of the contralateral pharyngeal recess (CPR) and the contralateral posterosuperior wall (CPSW) of the nasopharynx were obtained in each case and prepared for pathological examination. The factors associated with contralateral tumour infiltration were analysed. RESULTS: Five of 20 (25.0%) patients were pathologically confirmed to have carcinoma cell infiltration in the CPSW, including 2 (10.0%) that had carcinoma cell infiltration in the CPR. The T classification (P = 0.014) and primary tumour volume (P = 0.033) were positively associated with the infiltration of the CPSW, but none of the primary tumour factors affected the involvement of the CPR. The contralateral retropharyngeal lymph node (LN) metastasis (P = 0.016), but not the contralateral cervical LN, was significantly associated with the infiltration of the CPR. Positive Epstein-Barr virus DNA (EBV-DNA) was another factor that increased the probability of CPR invasion (P = 0.044). CONCLUSIONS: Contralateral pharyngeal recess infiltration is rare in patients with clinically diagnosed unilateral primary NPC. Reduced CTV coverage, including the CPSW but not CRP, is feasible for patients with unilateral cancer of the nasopharynx without contralateral LN metastasis or positive EBV-DNA. Further large-sample studies are needed.

6.
Oncotarget ; 8(44): 76189-76203, 2017 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-29100303

RESUMO

Keratin 8 (KRT8) plays an essential role in the development and metastasis of multiple human cancers. However, its role in clear cell renal cell carcinoma (ccRCC) remains unexplored. Here, we investigated the expression pattern, clinical significance, and function of KRT8 in ccRCC. KRT8 mRNA and protein levels were determined in two large cohorts using quantitative real-time polymerase chain reaction (qRT-PCR) and tissue microarray (TMA) immunohistochemistry (IHC), respectively. We found that KRT8 expression was upregulated in ccRCC and vein tumor thrombi (VTTs). KRT8 overexpression in ccRCC was significantly correlated with aggressive characteristics and was predictive of a poor prognosis in ccRCC patients. Moreover, KRT8 overexpression in renal cancer cell lines promoted cell migration and invasion. In contrast, KRT8 knockdown suppressed ccRCC metastasis both in vitro and in vivo. In addition, our findings showed that KRT8 promoted ccRCC metastasis by increasing IL-11 expression, causing IL-11 autocrine induction, and triggering STAT3 signaling. Overall, this study established the significance of KRT8-IL-11 axis activation in aggressive ccRCC and defined a novel critical signaling mechanism that drives human ccRCC invasion and metastasis.

7.
World J Gastroenterol ; 22(45): 9933-9943, 2016 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-28018100

RESUMO

Hepatocellular carcinoma (HCC) is one of the most lethal cancers, and its rate of incidence is rising annually. Despite the progress in diagnosis and treatment, the overall prognoses of HCC patients remain dismal due to the difficulties in early diagnosis and the high level of tumor invasion, metastasis and recurrence. It is urgent to explore the underlying mechanism of HCC carcinogenesis and progression to find out the specific biomarkers for HCC early diagnosis and the promising target for HCC chemotherapy. Recently, the reprogramming of cancer metabolism has been identified as a hallmark of cancer. The shift from the oxidative phosphorylation metabolic pathway to the glycolysis pathway in HCC meets the demands of rapid cell proliferation and offers a favorable microenvironment for tumor progression. Such metabolic reprogramming could be considered as a critical link between the different HCC genotypes and phenotypes. The regulation of metabolic reprogramming in cancer is complex and may occur via genetic mutations and epigenetic modulations including oncogenes, tumor suppressor genes, signaling pathways, noncoding RNAs, and glycolytic enzymes etc. Understanding the regulatory mechanisms of glycolysis in HCC may enrich our knowledge of hepatocellular carcinogenesis and provide important foundations in the search for novel diagnostic biomarkers and promising therapeutic targets for HCC.


Assuntos
Carcinoma Hepatocelular/metabolismo , Glucose/metabolismo , Glicólise/genética , Neoplasias Hepáticas/metabolismo , Fosforilação Oxidativa , Epigênese Genética , Genes Supressores de Tumor , Humanos , Mutação , Oncogenes , RNA não Traduzido , Transdução de Sinais
8.
Exp Gerontol ; 84: 88-95, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27612601

RESUMO

Accumulation of amyloid-ß (Aß) peptide and deposition of hyperphosphorylated tau protein are two major pathological hallmarks of Alzheimer's disease (AD). Glycogen synthase kinase-3ß (GSK3ß) is increasingly thought to play a pivotal role in the pathogenesis of AD, both as a regulator of the production of Aß and through its well-established role on tau phosphorylation. The phosphoinositide 3 kinase (PI3K)/Akt pathway plays an import role in neuronal survival and cognitive function, and is known as an upstream element of GSK3ß. Fuzhisan (FZS), a Chinese herbal complex prescription, has been used for the treatment of AD for over 20years, and is known to enhance the cognitive ability in AD patients as well as in AD model rats. However, it still remains unclear whether FZS is responsible for regulation of PI3K/AKT/GSK3ß signaling and contributes to subsequent down-regulation of Aß and phosphorylated tau. Thus, we treated APP/PS1 transgenic mice, a useful model of AD-related memory impairment, with FZS by intragastrical administration for 60days and Donepezil was used as a positive control. The results showed that treatment with FZS significantly reversed the memory deficit in the Tg APP/PS1 mice in the Morris water maze test. Moreover, FZS significantly attenuated Aß production through inhibition of APP procession and phosphorylation of tau in the hippocampus of Tg APP/PS1 mice. In addition, FZS treatment also increased PI3K and pSer473-AKT levels, inhibited GSK3ß activity by increasing phosphorylation of GSK3ß at Ser9. These results indicated that the memory ameliorating effect of FZS may be, in part, by regulation the PI3K/AKT/GSK3ß signaling which may contribute to down-regulation of Aß and tau hyperphosphorylation.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Hipocampo/efeitos dos fármacos , Transtornos da Memória/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Peptídeos beta-Amiloides/metabolismo , Animais , Western Blotting , Modelos Animais de Doenças , Donepezila , Quinase 3 da Glicogênio Sintase/metabolismo , Hipocampo/metabolismo , Indanos/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Piperidinas/administração & dosagem , Proteínas tau/metabolismo
9.
Neurochem Res ; 41(11): 3074-3082, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27518086

RESUMO

The pathological features of Alzheimer's disease (AD) include extracellular neuritic plaques containing ß-amyloid (Aß) peptide, a cleaved fragment of amyloid precursor protein (APP) via ß-site amyloid precursor protein-cleaving enzyme 1 (BACE1) and intracellular neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau. Cyclin-dependent kinase 5 (Cdk5) is increasingly thought to play a pivotal role in the pathogenesis of AD, both as a regulator of the production of Aß and through its well-established role as a tau kinase. Fuzhisan (FZS), a Chinese herbal complex prescription, has been used for the treatment AD for over 20 years, and is known to enhance the cognitive ability in AD patients as well as in AD model rats. To investigate mechanisms of AD and the potential therapy of FZS in AD, we treated senescence-accelerated mouse SAMP8 mice, a useful model of AD-related memory impairment, with FZS by intragastrical administration for 8 weeks and Donepizel was used as a positive control. The results showed that FZS (0.3, 0.6, and 1.2 g/kg/day) improved impaired cognitive ability of aged SAMP8 mice in a dose-dependent manner. FZS robustly decreased Aß level and phosphorylation of tau. This was accompanied by a significant decrease in the BACE1 level and phosphorylated APP (Thr668). Futhermore, The p25/Cdk5 pathway was markedly down-regulated by FZS treatment. These results indicated that the memory ameliorating effect of FZS may be, in part, by regulation the p25/Cdk5 pathway which may contribute to down-regulation of Aß and tau hyperphosphorylation.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/biossíntese , Medicamentos de Ervas Chinesas/farmacologia , Hipocampo/efeitos dos fármacos , Emaranhados Neurofibrilares/efeitos dos fármacos , Proteínas tau/metabolismo , Envelhecimento , Doença de Alzheimer/metabolismo , Animais , Quinase 5 Dependente de Ciclina/metabolismo , Modelos Animais de Doenças , Regulação para Baixo , Hipocampo/metabolismo , Masculino , Camundongos , Emaranhados Neurofibrilares/metabolismo , Fosforilação/efeitos dos fármacos
10.
Zhen Ci Yan Jiu ; 40(5): 383-7, 2015 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-26669195

RESUMO

OBJECTIVE: To observe the effect of acupuncture intervention at different time-points on the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), the content of malonaldehyde (MDA) and expression of heat shock protein 70 (HSP 70) of liver tissue in rats with simulated weightlessness, so as to explore its mechanism underlying improvement of liver injury in rats with simulated weightlessness. METHODS: Twenty male Wistar rats were randomly divided into control group, model group, pre-acupuncture group and EA group, 5 rats in each. The model of simulated weightlessness was established by tail suspension for 4 week. One week before the tail suspension, the rats in the pre-acupuncture group were treated with electroacupuncture (EA) at "Shenshu" (BL 23), "Pishu"(BL 20) and "Sanyinjiao" (SP 6) for 30 min before treatment, once a day for 7 days. The rats in the EA group received tail suspension and acupuncture intervention at the same time. EA was applied for 30 min per treatment, once every other day for 14 times. Immunohistochemical staining was used to assay the expression of HSP 70 in the liver tissue. The activities of SOD and GSH-PX and content of MDA in liver tissues were examined by means of colourimetric method. Results Compared with the control group,the expression of HSP 70 and the content of MDA in the liver tissue were increased significantly (P < 0.01), and the activity of SOD and GSH-PX was notably reduced (P < 0.05) in the model group. Compared with the model group, the content of HSP 70 was significantly reduced in the pre-acupuncture group (P < 0.01). There were no significant changes in the levels of SOD, GSH-PX, MDA and HSP 70 in the EA group (P > 0.05). In comparison with the pre-acupuncture group, the activity of GSH-PX was lower (P < 0.05) and the content of MDA was higher (P < 0.05) in the EA group. CONCLUSION: EA-pretreatment can suppress the increase of liver HSP 70 immunoactivity in rats with simulated weightlessness, being likely to improve the antioxidant ability of liver.


Assuntos
Eletroacupuntura , Glutationa Peroxidase/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Malondialdeído/metabolismo , Superóxido Dismutase/metabolismo , Ausência de Peso/efeitos adversos , Pontos de Acupuntura , Animais , Glutationa Peroxidase/genética , Proteínas de Choque Térmico HSP70/genética , Humanos , Fígado/lesões , Fígado/metabolismo , Masculino , Modelos Biológicos , Ratos , Ratos Wistar , Superóxido Dismutase/genética
12.
Tumour Biol ; 35(11): 11621-9, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25139094

RESUMO

Dystroglycan (DG), a multifunctional protein dimer of non-covalently linked α and ß subunits, is best known as an adhesion and transduction molecule linking the cytoskeleton and intracellular signaling pathways to extracellular matrix proteins. Loss of DG binding, possibly by degradation or disturbed glycosylation, has been reported in a variety of cancers. DG is abundant at astroglial endfeet forming the blood-brain barrier (BBB) and glia limitans; so, we examined if loss of expression is associated with glioma. Expression levels of α-DG and ß-DG were assessed by immunohistochemistry in a series of 78 glioma specimens to determine the relationship with tumor grade and possible prognostic significance. α-DG immunostaining was undetectable in 44 of 49 high-grade specimens (89.8%) compared to 15 of 29 low-grade specimens (51.72%) (P<0.05). Moreover, loss of α-DG expression was an independent predictor of shorter disease-free survival (DFS) (hazards ratio (HR) = 0.142, 95% confidence interval (CI) 0.033-0.611, P=0.0088). Reduced expression of both α-DG and ß-DG was also a powerful negative prognostic factor for DFS (HR=2.556, 95% CI 1.403-4.654, P=0.0022) and overall survival (OS) (HR=2.193, 95% CI 1.031-4.666, P=0.0414). Lack of α-DG immunoreactivity is more frequent in high-grade glioma and is an independent predictor of poor clinical outcome. Similarly, lack of both α-DG and ß-DG immunoreactivity is a strong independent predictor of clinical outcome.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/metabolismo , Distroglicanas/metabolismo , Glioma/metabolismo , Recidiva Local de Neoplasia/metabolismo , Adulto , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Feminino , Seguimentos , Glioma/mortalidade , Glioma/patologia , Humanos , Técnicas Imunoenzimáticas , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Gradação de Tumores , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
13.
Oncol Rep ; 32(4): 1734-40, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25109303

RESUMO

As a highly aggressive malignant disease, the prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) is poor. Yet, the mechanisms underlying the progression of PDAC remain unclear. MicroRNAs (miRNAs) may be involved in various human cancers as cancer suppressors or oncogenes. MicroRNA-183 (miR-183) was recently reported to be dysregulated in various types of cancer and to play an important role in the processes of cancer. However, the effects and potential mechanisms of action of miR-183 in PDAC have not been explored. In the present study, low expression of miR-183 was observed in PDAC tissues and cell lines. Low expression of miR-183 in PDAC was significantly associated with tumor grade, metastasis and TNM stage. Kaplan-Meier survival analysis demonstrated that patients harboring low expression of miR-183 had a significantly reduced overall survival than patients with a high level of miR-183 expression. The present study revealed that B-cell-specific Moloney murine leukemia virus insertion site 1 (Bmi-1) expression was inversely correlated with miR-183. Our findings also demonstrated that a low level of miR-183 expression effectively suppressed the growth of PDAC cells via regulation of Bmi-1. Following Bmi-1 silencing or upregulation of miR-183, the expression levels of cyclin D1, cyclin-dependent kinase (CDK)2 and CDK4 were decreased. It is reasonable to conclude that alteration of miR-183 expression may regulate the function of PDAC cells by the downregulation of Bmi-1 expression.


Assuntos
Carcinoma Ductal Pancreático/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética , MicroRNAs/genética , Neoplasias Pancreáticas/genética , Complexo Repressor Polycomb 1/genética , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Linhagem Celular Tumoral , Regulação para Baixo , Feminino , Técnicas de Silenciamento de Genes , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Complexo Repressor Polycomb 1/metabolismo , Prognóstico , Ensaio Tumoral de Célula-Tronco
14.
Int J Biol Sci ; 10(7): 664-76, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25013376

RESUMO

Long non-coding RNAs (lncRNAs) have previously been implicated in human disease states, especially cancer. Although the aberrant expression of lncRNAs has been observed in cancer, the biological functions and molecular mechanisms underlying aberrantly expressed lncRNAs in hepatocellular carcinoma (HCC) have not been widely established. In the present study, we investigated a novel lncRNA, termed URHC (up-regulated in hepatocellular carcinoma), and evaluated its role in the progression of HCC. Expression profiling using a lncRNA microarray revealed that URHC was highly expressed in 3 HCC cell lines compared to normal hepatocytes. Quantitative real-time polymerase chain reaction (qRT-PCR) analyses confirmed that URHC expression was increased in hepatoma cells and HCC tissues. Moreover, using qRT-PCR, we confirmed that URHC expression was up-regulated in 30 HCC cases (57.7%) and that its higher expression was correlated with poor overall survival. We further demonstrated that URHC inhibition reduced cell proliferation and promoted apoptosis. We hypothesize that URHC may function by regulating the sterile alpha motif and leucine zipper containing kinase AZK (ZAK) gene, which is located near URHC on the same chromosome. We found that ZAK mRNA levels were down-regulated in HCC tissues and the expression levels of ZAK were negatively correlated with those of URHC in the above HCC tissues. Next, we confirmed that URHC down-regulated ZAK, which is involved in URHC-mediated cell proliferation and apoptosis. Furthermore, ERK/MAPK pathway inactivation partially accounted for URHC-ZAK-induced cell growth and apoptosis. Thus, we concluded that high URHC expression can promote cell proliferation and inhibit apoptosis by repressing ZAK expression through inactivation of the ERK/MAPK pathway. These findings may provide a novel mechanism and therapeutic targets for the treatment of HCC.


Assuntos
Apoptose , Carcinoma Hepatocelular/genética , Proliferação de Células , Neoplasias Hepáticas/genética , Sistema de Sinalização das MAP Quinases , Proteínas Quinases/fisiologia , RNA Longo não Codificante/fisiologia , Linhagem Celular Tumoral , Humanos , MAP Quinase Quinase Quinases , Proteínas Quinases/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo
15.
Acta Otolaryngol ; 134(6): 631-5, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24646139

RESUMO

CONCLUSION: The epidermal growth factor receptor (EGFR) mutation is rare in patients with laryngeal squamous cell carcinoma (LSCC) in China. OBJECTIVE: To determine the incidence of EGFR mutations in patients with LSCC who underwent surgical resection in mainland China. METHODS: xTAG technology was used to detect the EGFR exon 19, exon 20, and exon 21 mutations in 132 patients with LSCC who underwent surgical treatment in our hospital from 2010 to 2013. RESULTS: Of the 132 LSCC specimens examined, only 1 specimen was found to be positive for EGFR exon 20 mutation (0.76%). The mutation was p.T790M in exon 20. Two LSCC specimens were positive for EGFR exon 21 mutation (1.52%). The mutation was p.L858R in exon 21. None of the samples was found to be positive for EGFR exon 19 mutation.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Carcinoma de Células Escamosas/genética , Receptores ErbB/genética , Neoplasias Laríngeas/genética , Mutação/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , China , Estudos de Coortes , Éxons/genética , Feminino , Humanos , Neoplasias Laríngeas/patologia , Neoplasias Laríngeas/cirurgia , Masculino , Pessoa de Meia-Idade
16.
Zhen Ci Yan Jiu ; 39(6): 443-7, 2014 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-25632567

RESUMO

OBJECTIVE: To observe the effect of electroacupuncture (EA) stimulation of "Neiguan" (PC 6) and "Sanyinjiao" (SP 6) on morphological changes, myocardial energy metabolism in rats undergoing simulated weightlessness. METHODS: A total of 40 male Wistar rats were randomly divided into normal control, weightlessness model, Neiguan (PC 6) and Sanyinjiao (SP 6) groups (10 rats/group). EA was applied to PC 6 and SP 6 acupoints for 30 min, once every other day. The morphological changes were observed by light microscopy after H. E. staining. Lactate dehydrogenase (LDH), succinate dehydrogenase (SDH) and ATPase activities in the left ventricular myocardium were measured by colorimetry. RESULTS: In weightlessness rats, myocardial pathological changes as loose arrangement, breakage and lytic necrosis of myocardial fibers were found, these changes were obviously improved in rats of both PC 6 and SP 6 groups. Compared with the control group, the ATPase activity was significantly decreased, while the LDH activity was significantly increased in the model group (P<0.05). After EA intervention, the ATPase activity was obviously increased in the SP 6 group (P<0. 05), and LDH activity was apparently reduced in both PC 6 and SP 6 groups (P<0. 05). No significant changes were found in myocardial SDH activity after modeling and EA of the two acupoints (P>0. 05). CONCLUSION: EA intervention has functions in up-regulating ATP activity and suppressing the myocardial LDH activity in weightlessness rats, which may be related to its effect in improving myocardial pathological changes.


Assuntos
Eletroacupuntura , Miocárdio/patologia , Ausência de Peso , Adenosina Trifosfatases/metabolismo , Animais , L-Lactato Desidrogenase/metabolismo , Masculino , Miocárdio/metabolismo , Ratos , Ratos Wistar
17.
Technol Cancer Res Treat ; 13(1): 77-86, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23862748

RESUMO

MiR-34a, a direct target of p53, has been shown to target several molecules associated with the cell cycle and cell survival pathways, and its dysregulation is implicated in cancer drug resistance or sensitivity in several human cancers. However, the correlation between miR-34a expression and chemoresistance has not been explored in HCC. In this study, we confirmed that miR-34a was significantly down-regulated in HCC tissues and HCC cell lines by qRT-PCR. HCC tissues with lower miR-34a expression displayed higher expression of Bcl-2 protein than those with high expression of miR-34a; therefore, an inverse correlation is evident between the miR-34a level and Bcl-2 expression. Moreover, patients with lower miR-34a expression had significantly poorer overall survival. Bioinformatics and luciferase reporter assays revealed that miR-34a binds the 3'-UTR of the Bcl-2 mRNA and represses its translation. Western blotting analysis and qRT-PCR confirmed that Bcl-2 is inhibited by miR-34a overexpression. Functional analyses indicated that the restoration of miR-34a reduced cell viability, promoted cell apoptosis and potentiated sorafenib-induced apoptosis and toxicity in HCC cell lines by inhibiting Bcl-2 expression. This study is the first to demonstrate that miR-34a induces sensitivity to the anti-tumor effect of sorafenib in human HCC cells, suggesting a potential role of miR-34a in the treatment of HCC.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , MicroRNAs/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Adulto , Idoso , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Masculino , Pessoa de Meia-Idade , Niacinamida/administração & dosagem , Niacinamida/análogos & derivados , Compostos de Fenilureia/administração & dosagem , Proteínas Proto-Oncogênicas c-bcl-2/genética , Sorafenibe
18.
Zhongguo Zhen Jiu ; 34(11): 1106-10, 2014 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-25675574

RESUMO

OBJECTIVE: To explore the effects of pre-acupuncture and immediate acupuncture on kidney function and oxygen free radical metabolism in rats with simulated weightlessness. METHODS: Twenty male clean-grade Wister rats were randomly divided into a normal control group, a model group, a pre-acupuncture group and an immediate acupuncture group, 5 rats in each one. The rats in the normal control group did not receive any treatment but free activities for 4 weeks. The rats in the rest groups received 4-week tail suspension to establish the model of simulated weightlessness. One week before the tail suspension, the rats in the pre-acupuncture group were treated with electroacupuncture at "Shenshu" (BL 23), "Pishu" (BL 20) and "Sanyinjiao" (SP 6) for 30 min per treatment, once a day for 7 days. The rats in the immediate acupuncture group received tail suspension and acupuncture at the same time; during the tail suspension, the electroacupuncture was applied at "Shenshu" (BL 23), "Pishu" (BL 20) and "Sanyinjiao" (SP 6) for 30 min per treatment, once every other day for 14 days. The colorimetric method was used to measure the content of blood urea nitrogen (BUN) in serum as well as activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) and content of malonaldehyde (MDA) in renal tissue in each group. RESULTS: Compared with the normal control group, the content of BUN in the model group was increased significantly (P<0.01), the activity of SOD and GSH-PX in nephridial tissue was significantly reduced (both P<0.01), and the content of MDA was increased significantly (P<0.05). Compared with the model group, the content of BUN in the pre-acupuncture group and immediate acupuncture group was significantly reduced (P<0.01, P<0.05), the activity of GSH-PX in the pre-acupuncture group was obviously increased (P<0.05) and the content of MDA in the immediate acupuncture group was increased significantly (P<0.01). Compared with the immediate acupuncture group, the content of MDA in the pre-acupuncture group was lower (P<0.01). CONCLUSION: The pre-acupuncture and immediate acupuncture both have the capacity to improve the kidney function and anti-oxygen free radical injury in rats with simulated weightlessness, however, the capacity to increase the protection ability of the kidney and eliminate free radical in the pre-acupuncture group is superior to that in the immediate acupuncture group, which is likely to be related with improving antioxidant ability of kidney.


Assuntos
Pontos de Acupuntura , Terapia por Acupuntura , Nefropatias/fisiopatologia , Nefropatias/terapia , Rim/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Ausência de Peso/efeitos adversos , Animais , Antioxidantes/metabolismo , Humanos , Nefropatias/metabolismo , Masculino , Malondialdeído/metabolismo , Ratos , Ratos Wistar , Voo Espacial , Superóxido Dismutase/metabolismo
20.
Ann Hepatol ; 12(5): 815-21, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24018501

RESUMO

BACKGROUND: We have previously reported that Notch signaling pathway protects hepatocytes from ischemia/ reperfusion (I/R) injury by repressing reactive oxygen species (ROS) production. However, apart from hepatocytes, non-parenchymal cells including vascular endothelia cells, Kupffer cells and hepatic stellate cells are also reported to be involved in hepatic I/R injury. AIM: To clarify the role of Notch signaling in non-parenchymal cells subjected to I/R injury. MATERIALS AND METHODS: Human Umbilical Vein Endothelial Cells (HUVECs), mouse macrophage line RAW264.7 and rat hepatic stellate cell line HSC-T6 were cultured and subjected to I/R injury, respectively. Activation of Notch signaling was assessed by NICD western blot. Then, pharmacological inhibitor (γ-secretase inhibitor GSI) was used to block Notch signaling of related cell lines in vitro. Intracellular ROS was detected and analyzed by FACS and apoptosis was examined by TUNEL staining and Annexin V staining. RESULTS: Notch signaling responded to I/R injury and I/R injury induced activation of Notch signaling in nonparenchymal cells. Notch signal deficiency led to overproduction of ROS and aggravated cell death of non-parenchymal cells subjected to I/R injury. CONCLUSION: Notch signal protects non-parenchymal cells from I/R injury by repressing ROS.


Assuntos
Hepatopatias/prevenção & controle , Fígado/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Receptores Notch/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Transdução de Sinais , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Secretases da Proteína Precursora do Amiloide/metabolismo , Animais , Apoptose , Linhagem Celular , Inibidores Enzimáticos/farmacologia , Células Estreladas do Fígado/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Fígado/efeitos dos fármacos , Fígado/patologia , Hepatopatias/metabolismo , Hepatopatias/patologia , Macrófagos/metabolismo , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Ratos , Receptores Notch/antagonistas & inibidores , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Transdução de Sinais/efeitos dos fármacos
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