p63 protein

  • 文章类型: Journal Article
    导管消融术已被证明可以减少心房颤动(AF)的复发。导管消融术后房颤复发的机制尚不清楚,本研究旨在确定与房颤复发相关的血清蛋白。本前瞻性研究包括一组房颤患者,随访1年后分为两组:第1组包括导管消融术后发生代偿性房颤的患者,第2组包括导管消融术后发生房颤复发的患者。在分别从第1组和第2组招募的M1和M2小亚组中进行血清蛋白的初始微阵列分析。通过抗体微阵列来评估潜在的相关蛋白质。初始蛋白质组分析的数据鉴定了组1和组2中的候选蛋白质,然后通过ELISA测量它们的水平。分析的数据表明,M2亚组中RAD51和p63蛋白水平与M1亚组相比总体增加,表明这两种蛋白与房颤复发的潜在相关性。第1组和第2组的RAD51和p63水平的ELISA结果表明,与第1组相比,第2组(AF复发或基质AF)的RAD51(11.11±4.36vs8.45±4.85ng/mL;P=0.009)和p63(165.73±113.75vs标准化光密度100.05±37.56单位;P=0.0007)的水平增加(补偿)。因此,RAD51和p63与导管消融术后房颤复发相关,并可能代表后续结局的可能病因因素。
    Catheter ablation has been demonstrated to reduce atrial fibrillation (AF) recurrence. The mechanisms of AF recurrence after catheter ablation are unknown, and the present study aimed to identify serum proteins associated with AF recurrence. The present prospective study comprised a cohort of patients with AF, which was divided into two groups after one-year follow-up: group 1 included patients with compensated AF after catheter ablation and group 2 included patients with AF recurrence after catheter ablation. Initial microarray profiling of the serum proteins was performed in small subgroups M1 and M2 recruited from groups 1 and 2, respectively, by an antibody microarray to evaluate potentially relevant proteins. The data of initial proteomic profiling identified candidate proteins in groups 1 and 2, and their levels were then measured by ELISA. The data of profiling suggested an overall increase in the levels of RAD51 and p63 proteins in the M2 subgroup versus that in the M1 subgroup, indicating potential relevance of these two proteins to AF recurrence. The results of ELISA of the levels of RAD51 and p63 in the groups 1 and 2 demonstrated an increase in the levels of RAD51 (11.11 ± 4.36 vs 8.45 ± 4.85 ng/mL; P = 0.009) and p63 (165.73 ± 113.75 vs 100.05 ± 37.56 units of normalized optical density; P = 0.0007) in the group 2 (with AF recurrence or substrate AF) compared with that in the group 1 (compensated AF). Thus, RAD51 and p63 were associated with AF recurrence after catheter ablation and may represent possible etiological factors for subsequent outcomes.
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  • 文章类型: Journal Article
    这项研究的目的是比较p63蛋白和钙蛋白对犬乳腺肿瘤中肌上皮细胞的亲和力和特异性的表达。研究的材料包括10例良性和32例恶性乳腺肿瘤,这些肿瘤来自接受乳房切除术治疗的雌性犬。针对p63蛋白克隆4A4和钙蛋白克隆CALP的原代小鼠单克隆抗体用于免疫组织化学反应的单染色和双染色系统。研究表明,良性肿瘤和原位癌中的大多数肌上皮细胞对两种标志物均表现出强烈的阳性标记。在其他恶性肿瘤中,在静息肌上皮细胞(MEC)和肥大肌上皮细胞(HMEC)中观察到强烈的免疫反应性,而梭形星状肌上皮细胞(SMEC)和圆形肌上皮细胞(RMEC)的免疫反应性中等。仅在肌上皮细胞中观察到p63蛋白的颗粒扩散核表达。就Calponin而言,不仅在肌上皮细胞中,而且在一些基质成纤维细胞和血管平滑肌细胞中也注意到弥漫性细胞质表达。上皮细胞未显示所研究标记物的特异性表达。获得的结果表明,与calponin相比,p63是犬乳腺肿瘤中肌上皮细胞的敏感且更特异的标记。这些发现表明,使用p63进行的免疫组织化学分析可能是犬乳腺肿瘤常规组织学检查的有价值的补充,有助于鉴定具有肌上皮成分的肿瘤。
    The aim of this study was to compare the expression of p63 protein and calponin in terms of their affinity and specificity for myoepithelial cells in canine mammary tumours. The studied material included 10 benign and 32 malignant mammary tumours from female dogs treated with mastectomy. Primary mouse monoclonal antibodies directed against p63 protein clone 4A4 and calponin clone CALP were used in single- and doublestain system of immunohistochemical reaction. The investigations have shown that majority of myoepithelial cells in benign tumours and carcinomas in situ exhibited strong positive labelling for both markers. In other malignant tumours strong immunoreactivity was observed in resting myoepithelial cells (MECs) and hypertrophic myoepithelial cells (HMECs), while the immunoreactivity in spindle-stellate myoepithelial cells (SMECs) and rounded myoepithelial cells (RMECs) was moderate. The granular-diffuse nuclear expression of p63 protein was observed only in myoepithelial cells. In terms of calponin, diffuse cytoplasmic expression was noted not only in myoepithelial cell but also in some stromal fibroblasts and vascular smooth muscle cells. The epithelial cells did not exhibit specific expression of the investigated markers. The obtained results indicate that p63 is a sensitive and more specific marker of myoepithelial cells in canine mammary tumours compared with calponin. These findings suggest that the immunohistochemical analysis peformed with the use of p63 can be a valuable complement of routine histological examinations of canine mammary tumours facilitating identification of tumours with myoepithelial component.
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  • 文章类型: Case Reports
    Ankyloblepharon filiforme adnatum associated with Hay-Wells syndrome is a rare congenital disease caused by mutations in TP63 gene on the 3q27 chromosome. Here, we report a case of a new-born suffering from this syndrome in whom we detected a mutation c.1709T>C not previously included in the Ensemble database.
    A girl delivered in the 34th week of gestation from a physiological pregnancy was born with extensive burn-like skin defects, ankyloblepharon filiforme adnatum, palate cleft, onychodystrophy of all limbs and syndactyly of toes. Hay-Wells syndrome was suspected and confirmed by genetic examination. A heterozygous missense change c.1709T>C was found in the TP63 gene. This variant leads to a 570th codon exchange of leucine for proline (p.Leu570Pro) on the protein level. The eyelid separation was performed surgically, burns were treated locally and cosmetic surgeries correcting other defects are planned for the near future. The girl is still monitored by a multidisciplinary team.
    The mutation was not previously described in the literature or databases and should be included into these as probably pathogenic. A multidisciplinary approach is necessary to care for a patient with Hay-Wells syndrome, such care however can provide good results.
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  • 文章类型: Case Reports
    Ankyloblepharon-ectodermal dysplasia-cleft lip/palate (AEC) syndrome is a disorder resulting from anomalous embryonic development of ectodermal tissues. There is evidence that AEC syndrome is caused by mutations in the TP63 gene, which encodes the p63 protein. This is an important regulatory protein involved in epidermal proliferation and differentiation.
    Genome sequencing was performed in DNA from peripheral blood leukocytes of a newborn with AEC syndrome and her parents. Variants were searched in all coding exons and intron-exon boundaries of the TP63 gene.
    A heterozygous missense variant (NM_003722.4:c.1063G>C (p.Asp355His) was found in the newborn patient. No variants were found in either of the parents.
    We identified a previously unreported variant in TP63 gene which seems to be involved in the somatic malformations found in the AEC syndrome. The absence of this variant in both parents suggests that the variant appeared de novo.
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  • 文章类型: Journal Article
    低水平激光治疗(LLLT)已被广泛用于改善上皮伤口愈合,尽管LLLT后上皮成熟和分层的确切反应尚不清楚。因此,这项研究旨在评估用LLLT治疗时角质形成细胞(KCs)的体外生长和分化以及体内伤口愈合反应。人KC(HaCaT细胞)在所有使用的激光能量密度(3、6和12J/cm(2),660nm,100mW),以及细胞周期蛋白D1的表达增加。此外,与上皮增殖和成熟相关的蛋白质(p63,CK10,CK14)的免疫表达均表明LLLT治疗的伤口中迁移的KC成熟更快。这样,LLLT利用所采用的参数促进了上皮愈合的改善;与上皮增殖和成熟相关的几种蛋白质表达的变化证实了这种改善。细胞角蛋白10(红色)和细胞周期蛋白D1(绿色)在(A)对照角质形成细胞和(B)低水平激光照射细胞中的免疫荧光表达。蓝色表示细胞的细胞核(DAPI染色)。
    Low-level laser therapy (LLLT) has been extensively employed to improve epithelial wound healing, though the exact response of epithelium maturation and stratification after LLLT is unknown. Thus, this study aimed to assess the in vitro growth and differentiation of keratinocytes (KCs) and in vivo wound healing response when treated with LLLT. Human KCs (HaCaT cells) showed an enhanced proliferation with all the employed laser energy densities (3, 6 and 12 J/cm(2) , 660 nm, 100 mW), together with an increased expression of Cyclin D1. Moreover, the immunoexpression of proteins related to epithelial proliferation and maturation (p63, CK10, CK14) all indicated a faster maturation of the migrating KCs in the LLLT-treated wounds. In that way, an improved epithelial healing was promoted by LLLT with the employed parameters; this improvement was confirmed by changes in the expression of several proteins related to epithelial proliferation and maturation. Immunofluorescent expression of cytokeratin 10 (red) and Cyclin D1 (green) in (A) Control keratinocytes and (B) Low-level laser irradiated cells. Blue color illustrates the nuclei of the cells (DAPI staining).
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