RESUMEN
Objective:To investigate the role of CD4 ⺠CD25 ⺠T regs and CCL17 and CCL22 in the pathogenesis of HNSCC.Method:Twenty cases of HNSCC were enrolled. All patients were primary or recurrent after treatment (chemotherapy, surgery). The primary tumor was taken as the experimental group, and the adjacent normal tissues from the primary tumor 1-3 cm were taken as control group. CD4 ⺠/Foxp3 and CD25âº/Foxp3 were detected by immunofluorescence, while CCL17 and CCL22 were detected by ELISA. The difference and correlation between the amount of CD4âº,CD25⺠and the expression of CCL17, CCL22 were observed and analyzed.Result:The difference of mean optical density between CD4âº/Foxp3 and CD25âº/Foxp3 was statistically significant between the experimental group and the control group (P<0.05). The concentration of CCL17 and CCL22 was statistically different between the two groups (P<0.01). There was a positive correlation between CD25âºand CCL17,CCL22(r=0.595, 0.720,P<0.01).Conclusion:CD4âºCD25âºT regs and CCL17,CCL22 played an important role in the pathogenesis of head and neck squamous cell carcinoma,both of which interacted with each other,and promoted the recurrence and metastasis of HNSCC.
Asunto(s)
Carcinoma de Células Escamosas/inmunología , Quimiocina CCL17/fisiología , Quimiocina CCL22/fisiología , Neoplasias de Cabeza y Cuello/inmunología , Linfocitos T Reguladores , Antígeno CD24 , Carcinoma de Células Escamosas/patología , Factores de Transcripción Forkhead , Neoplasias de Cabeza y Cuello/patología , Humanos , Subunidad alfa del Receptor de Interleucina-2Asunto(s)
Factor Neurotrófico Derivado del Encéfalo/sangre , Factor Neurotrófico Derivado del Encéfalo/genética , Regulación de la Expresión Génica , Metionina/genética , Polimorfismo de Nucleótido Simple/genética , Trastornos por Estrés Postraumático/sangre , Trastornos por Estrés Postraumático/genética , Valina/genética , Adolescente , Adulto , Campaña Afgana 2001- , Animales , Modelos Animales de Enfermedad , Femenino , Genotipo , Humanos , Guerra de Irak 2003-2011 , Masculino , Persona de Mediana Edad , Personal Militar , Escalas de Valoración Psiquiátrica , Ratas , Reflejo de Sobresalto , Trastornos por Estrés Postraumático/etiología , Adulto JovenRESUMEN
Substantial evidence suggests that the accumulation of beta-amyloid (Abeta)-derived peptides contributes to the aetiology of Alzheimer's disease (AD) by stimulating formation of free radicals. Thus, the antioxidant alpha-lipoate, which is able to cross the blood-brain barrier, would seem an ideal substance in the treatment of AD. We have investigated the potential effectiveness of alpha-lipoic acid (LA) against cytotoxicity induced by Abeta peptide (31-35) (30 microM) and hydrogen peroxide (H(2)O(2)) (100 microM) with the cellular 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) reduction and fluorescence dye propidium iodide assays in primary neurons of rat cerebral cortex. We found that treatment with LA protected cortical neurons against cytotoxicity induced by Abeta or H(2)O(2). In addition, LA-induced increase in the level of Akt in the neurons was observed by Western blot. The LA-induced neuroprotection and Akt increase were attenuated by pre-treatment with the phosphatidylinositol 3-kinase inhibitor, LY294002 (50 microM). Our data suggest that the neuroprotective effects of the antioxidant LA are partly mediated through activation of the PKB/Akt signaling pathway.
Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Antioxidantes/farmacología , Muerte Celular/efectos de los fármacos , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Proteínas Serina-Treonina Quinasas , Proteínas Proto-Oncogénicas/efectos de los fármacos , Ácido Tióctico/farmacología , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/fisiopatología , Péptidos beta-Amiloides/antagonistas & inhibidores , Péptidos beta-Amiloides/metabolismo , Animales , Bioensayo , Muerte Celular/fisiología , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Células Cultivadas/efectos de los fármacos , Células Cultivadas/metabolismo , Células Cultivadas/patología , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/metabolismo , Corteza Cerebral/fisiopatología , Colorantes , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas/fisiología , Feto , Peróxido de Hidrógeno/antagonistas & inhibidores , Peróxido de Hidrógeno/metabolismo , Neuronas/metabolismo , Neuronas/patología , Fragmentos de Péptidos/antagonistas & inhibidores , Fragmentos de Péptidos/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas c-akt , Ratas , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Sales de Tetrazolio , TiazolesRESUMEN
The use of rapid amplification of 5'-cDNA ends-PCR yielded two novel sequences for the rat orphan receptor, TR4, representing heterogeneity on the 5'-untranslated region. Genomic structure analysis revealed that the 5'-untranslated region of the longer messenger RNA fragment, rTR4-1, contained three exons, alpha, beta, and gamma. The skipping of exon gamma gave rise to rTR4-2, indicating that rTR4-1 and rTR4-2 are products of alternative splicing. We isolated another novel rat TR4 splice variant, rTR4-NS, which was found to diverge from rTR4-2 at codon 504. rTR4-NS contained an unspliced intronic sequence with in-frame codons for eight amino acids followed by a termination codon. The three TR4 messenger RNA variants were differentially expressed. rTR4-NS appeared to be a rare transcript found in limited areas of the brain. In situ hybridization detect prominent TR4 signals in brain areas known to be involved in stress response. In cerebellar granule cells, the rise in TR4 expression correlated with the progression of neuronal maturation. N-Methyl-D-aspartate treatment triggered a marked increase in TR4 expression. These results suggest a possible role for TR4 in neuronal differentiation.
Asunto(s)
Variación Genética , Proteínas del Tejido Nervioso/genética , Empalme del ARN , Receptores de Esteroides/genética , Receptores de Hormona Tiroidea , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Northern Blotting , Encéfalo/metabolismo , Expresión Génica , Humanos , Hibridación in Situ , Masculino , Datos de Secuencia Molecular , N-Metilaspartato/farmacología , Proteínas del Tejido Nervioso/química , Reacción en Cadena de la Polimerasa , ARN Mensajero/química , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Receptores de Esteroides/químicaRESUMEN
We have developed a PCR-based method to detect, display and directly sequence multiple members of the nuclear hormone receptor (NHR) gene family. Our approach employs the basic concepts of RNA fingerprinting (Welsh et al. (1992) Nucleic Acids Res. 20, 4965-4970; Stone, B. and Wharton, W. (1994) Nucleic Acids Res. 22, 2612-2618) and differential display PCR (Liang, P. and Pardee, A.B. (1992) Science 257, 967-971), with modifications. In contrast to the previous methods, two conserved regions within the gene family were targeted to derive primers for PCR amplification. One of the conserved sites was used to deduce primers for cDNA synthesis. We believe that this strategy led to increased specificity. The use of degenerate primers with low redundancy in both reverse transcription and PCR steps also contributed to enhanced signal-to-noise ratio. The ability to directly sequence the amplified fragments constitutes a vast improvement over the previous methods. This method permitted the successful identification and simultaneous display of six different NHR genes, which included the previously unreported rat homolog of COUP-TFI and a recently described orphan receptor. We believe that this approach provides a convenient and rapid screening method for detecting and characterizing members of a gene family.