Homeobox gene DLX4 expression is increased in idiopathic human fetal growth restriction

Idiopathic fetal growth restriction (FGR) is often associated with placental insufficiency. Previously, we isolated and characterized homeobox gene DLX4 from the placenta and provided evidence that DLX4 may regulate placental development. Here, we have investigated whether DLX4 expression levels were altered in idiopathic FGR. FGR-affected placentae were collected based on strict clinical criteria. DLX4 mRNA expression was analysed in placentae obtained from pregnancies complicated by idiopathic FGR and gestation-matched control pregnancies (n = 25 each). Initial RT-PCR results showed a qualitative increase in DLX4 mRNA in both FGR-affected placentae and gestation-matched controls. Real-time PCR showed a 3-fold increase in DLX4 mRNA levels in FGR-affected placentae compared with gestation-matched controls (P < 0.005). Western immunoblotting using a rabbit DLX4 polyclonal antibody revealed significantly increased levels of DLX4 protein in term FGR-affected placentae compared with term controls [5500.1 +/- 21.8 (n = 10) versus 3533.2 +/- 22.4 (n = 10); P < 0.001]. Qualitative immunohistochemical analyses of term placentae showed moderately increased immunoreactivity for DLX4 antigen in the FGR-affected placentae in syncytiotrophoblasts, residual cytotrophoblast cells and endothelial cells of the fetal capillaries compared with gestation-matched control term placentae. We conclude that the increased expression of homeobox gene DLX4 may be a contributing factor to the developmental abnormalities seen in the FGR-affected placentae.     

同源异型盒基因DLX4在妊娠期高血压疾病中的表达研究

目的:检测妊娠期高血压疾病胎盘组织中同源异型盒基因DLX4的表达,探讨其在妊娠期高血压疾病发生、发展中的意义。方法:严格设置病例组和对照组,采用半定量逆转录聚合酶链反应法(RT-PCR)和免疫组化SABC法检测40例胎盘组织中DLX4mRNA和蛋白的表达情况。结果:DLX4 mRNA在子痫前期胎盘组织中的表达(轻度为0.17±0.05、重度为0.09±0.03)明显低于对照组(0.49±0.07,P<0.001)。DLX4蛋白在子痫前期胎盘中表达与对照组相比也显著降低(P<0.001)。结论:随着妊娠期高血压疾病临床症状的加重,胎盘组织中DLX4的表达呈明显下降趋势,同源异型盒基因DLX4参与了妊娠期高血压疾病胎盘的发育障碍及功能缺陷。     

BMP-2对室管膜前下区神经干细胞向多巴胺能神经元分化及对DLX5表达的影响

目的 探讨骨形成蛋白2(bone morphogenetic protein-2,BMP-2)对室管膜前下区(anterior subventricular zone,SVZa)神经干细胞(neural stem cells,NSCs)向多巴胺能神经元分化及对DLX5表达的影响.方法 体外培养SVZa NSCs,分为对照组、BMP-2组、BMP-2+Noggin组和Noggin组,通过免疫荧光染色和流式细胞术,观察其分化为酪氨酸羟化酶阳性(TH+)神经元的情况;用RT-PCR检测DIX5 mRNA表达水平.结果 BMP-2组SVZa NSCs向TH+神经元分化的比例和DLX5 mRNA表达水平均显著高于对照组(P<0.05),且这种效应能被其拮抗剂Noggin特异性抑制.结论 BMP-2可能通过上调DLX5表达水平从而促进SVZa NSCs向多巴胺能神经元分化.     

Thickness and microhardness of deciduous tooth enamel with known DLX3 mutation

Aim

To investigate the thickness and hardness of teeth affected by a 2-bp deletion (c.561_562delCT) in the DLX3 gene.

Methods and materials

Extracted maxillary deciduous second molar was collected from the affected individual at age 12 years 7 months. Samples were sectioned buccolingually after embedding in epoxy resin. We measured the enamel thickness and microhardness and performed an elemental analysis using an electron probe microanalyser.

Results

On average, the hardness of the enamel with a 2-bp deletion in DLX3 was about 53% of normal enamel hardness. The mutant enamel thickness was about half of the thickness of the normal control. The calcium level in the enamel with the 2-bp deletion was slightly decreased, while the magnesium level was slightly increased, in comparison to levels measured for normal teeth.

Conclusion

This study shows that enamel affected by a 2-bp deletion in DLX3 has reduced thickness as well as diminished microhardness. These data may explain the severe attrition and interdental spacing observed in affected individuals.     

DLX3基因罕见变异与发育性髋关节发育不良

目的:筛查DLX3基因(NM_005220)中发育性髋关节发育不良(DDH)相关的致病变异。方法:本研究对192例DDH患者和188例健康对照组的DLX3基因全部外显子区进行Sanger测序,排除已知高频单核苷酸多态性(SNP)位点(最小等位基因频率MAF≥1%)和对照组中存在的变异位点,结合功能性预测和保守性分析,最终筛选出DDH候选致病变异。结果:经过分析,最终在一个DDH患者中筛选出一个错义杂合变异DLX3c.G736C:p.D246H(rs3744539)可能为其致病突变,此变异在物种进化过程中高度保守且致病的可能性较高。结论:本研究首次对DLX3整个外显子区进行变异筛查,并发现新的DDH候选致病变异p.D246H。     

丹参酮调控LncRNA DLX6-AS1对LPS诱导的肺泡Ⅱ型上皮细胞损伤的作用

目的 探讨丹参酮对脂多糖(LPS)诱导的肺泡Ⅱ型上皮细胞损伤的影响及其可能作用机制.方法 采用LPS诱导的肺泡Ⅱ型上皮细胞建立急性肺损伤模型,随机分组:空白对照组、LPS组、LPS+丹参酮L组、LPS+丹参酮M组、LPS+丹参酮H组、LPS+si-NC组、LPS+si-DLX6-AS1组、LPS+丹参酮+pcDNA-D...     

Morphological analyses and a novel de novo DLX3 mutation associated with tricho–dento–osseous syndrome in a Chinese family

Tricho–dento–osseous (TDO) syndrome, an autosomal‐dominant disorder, affects the morphological appearance of the tooth enamel, hair, and bone. Previous studies have confirmed that mutations in the DLX3 gene are responsible for TDO. In this study, we describe a Chinese patient with the typical traits of TDO – kinky hair, enamel hypoplasia, skull and jaw bones thickening, and sclerosis. Unfortunately, as a result of excessive attrition, we were unable to assess taurodontism. Examination of the tooth ground section showed a thin layer of enamel with no rods on the patient's tooth and abnormalities in Tomes' granular layer and the dentinal tubules. Scanning electron microscopy and energy‐dispersive X‐ray spectroscopy of the tooth enamel showed significant differences between the patient and the control individuals. A hair sample from the patient observed under a laser‐scanning microscope showed longitudinal grooves in the hair shaft. Dual‐energy X‐ray absorptiometry measurement showed that the bone mineral density values of the patient's bones was much higher than normal. Finally, genetic analysis revealed a novel de novo missense mutation c.533A>G (p.Q178R) in the conserved homeodomain of the DLX3 gene. This DLX3 mutation is the sixth causative mutation for TDO to be identified so far.     

Common genetic variation in the GAD1 gene and the entire family of DLX homeobox genes and autism spectrum disorders

Biological and positional evidence supports the involvement of the GAD1 and distal‐less homeobox genes (DLXs) in the etiology of autism. We investigated 42 single nucleotide polymorphisms in these genes as risk factors for autism spectrum disorders (ASD) in a large family‐based association study of 715 nuclear families. No single marker showed significant association after correction for multiple testing. A rare haplotype in the DLX1 promoter was associated with ASD (P‐value = 0.001). Given the importance of rare variants to the etiology of autism revealed in recent studies, the observed rare haplotype may be relevant to future investigations. Our observations, when taken together with previous findings, suggest that common genetic variation in the GAD1 and DLX genes is unlikely to play a critical role in ASD susceptibility. © 2010 Wiley‐Liss, Inc.     

Therapeutic approaches to myeloma bone disease: an evolving story

Bone disease is a major morbidity factor in patients with multiple myeloma and significantly affects their overall survival. A complex interplay between malignant plasma cells and other marrow cells results in the generation of a microenvironment capable of enhancing both tumor growth and bone destruction. Bisphosphonates have consistently reduced the incidence of skeletal-related events in patients with multiple myeloma and other osteotropic tumors as well. However, their use is burdened with side-effects, including the risks of osteonecrosis of the jaw and kidney failure, suggesting that they should be discontinued after prolonged administration. New molecular targets of cell cross-talk in myeloma bone marrow are therefore under intensive investigation and new drugs are being explored in preclinical and clinical studies of myeloma bone disease. Compounds targeting osteoclast activation pathways, such as receptor activator of nuclear factor-κB/receptor activator of nuclear factor-κB ligand/osteoprotegerin, B-cell activating factor, mitogen-activated protein kinase and macrophage inflammatory protein-1α/chemokine receptor for macrophage inflammatory protein-1α axes, or soluble agents that improve osteoblast differentiation by modulating specific inhibitors such as Dickkopf-1 and transforming growth factor-β, as well as novel approaches of cytotherapy represent a new generation of promising drugs for the treatment of myeloma bone disease.     

长链非编码RNA DLX6-AS1 与微小RNA-346在糖尿病足72 例血清中的表达及其临床意义

目的探讨长链非编码RNA(lncRNA)DLX6-AS1与微小RNA(miR)-346在糖尿病足病人血清中的表达及其临床意义。方法收集2017年5月至2018年12月南阳市中心医院收治的72例糖尿病足病人为糖尿病足组,选取同期该院收治的60例2型糖尿病无糖尿病足病人为糖尿病组,取同期于该院进行健康体检的健康志愿者55例作为对照组。实时荧光定量逆转录聚合酶链反应(qRT-PCR)检测各组受检者血清中DLX6-AS1、miR-346的表达水平;采用酶联免疫吸附测定(ELISA)检测血管细胞黏附分子-1(VCAM-1)、成纤维细胞生长因子2(FGF2)、肿瘤坏死因子-α(TNF-α)水平;采用电化学发光法检测血清中白细胞介素-6(IL-6)水平;采用Pearson相关性分析检验糖尿病足病人血清DLX6-AS1、miR-346的表达水平与炎性因子的相关性;采用logistic回归分析研究影响糖尿病足发生的相关因素。结果糖尿病组、糖尿病足组病人VCAM-1、FGF2、TNF-α、IL-6水平高于对照组(P<0.05),糖尿病组与糖尿病足组比较差异有统计学意义(P<0.05);对照组DLX6-AS1的表达量是1.01±0.13,低于糖尿病组、糖尿病足组DLX6-AS1的表达量2.16±0.25、3.20±1.03(P<0.05);对照组miR-346的表达水平是1.00±0.16,高于糖尿病组、糖尿病足组miR-346的表达水平0.73±0.11、0.41±0.08(P<0.05),糖尿病组与糖尿病足组相比差异有统计学意义(P<0.05);随着糖尿病足病人Wagner分级增加DLX6-AS1的表达水平显著升高(P<0.05),miR-346的表达水平显著降低(P<0.05);DLX6-AS1的表达与FGF2、TNF-α、IL-6呈正相关(P<0.05),而miR-346与之呈负相关(P<0.05);DLX6-AS1与miR-346表达量是影响糖尿病足发生的危险因素(P<0.05)。结论糖尿病足病人血清中DLX6-AS1表达量升高,而miR-346表达量降低,二者可能参与糖尿病足发生及发展过程,并可能作为临床诊断的分子标志物。