House-dust mite allergen and ozone exposure decreases histamine H3 receptors in the brainstem respiratory nuclei

Allergic airway diseases in children are a common and a growing health problem. Changes in the central nervous system (CNS) have been implicated in contributing to some of the symptoms. We hypothesized that airway allergic diseases are associated with altered histamine H3 receptor expression in the nucleus tractus solitarius (NTS) and caudal spinal trigeminal nucleus, where lung/airway and nasal sensory afferents terminate, respectively. Immunohistochemistry for histamine H3 receptors was performed on brainstem sections containing the NTS and the caudal spinal trigeminal nucleus from 6- and 12-month-old rhesus monkeys who had been exposed for 5 months to house dust mite allergen (HDMA) + O₃ or to filtered air (FA). While histamine H3 receptors were found exclusively in astrocytes in the caudal spinal trigeminal nucleus, they were localized to both neuronal terminals and processes in the NTS. HDMA + O₃ exposure significantly decreased histamine H3 receptor immunoreactivity in the NTS at 6 months and in the caudal spinal trigeminal nucleus at 12 months of age. In conclusion, exposing young primates to HDMA + O₃ changed histamine H3 receptor expression in CNS pathways involving lung and nasal afferent nerves in an age-related manner. Histamine H3 receptors may be a therapeutic target for allergic asthma and rhinitis in children.     

Autoantibodies reacting with vasopressin and oxytocin in relation to cortisol secretion in mild and moderate depression

Background

Abnormal vasopressin (VP) and oxytocin (OT) signaling may contribute to the altered activity of the hypothalamo-pituitary-adrenal (HPA) axis in major depression; however, the underlying mechanisms remain uncertain. This study characterized plasma levels and affinities of OT- and VP-reactive autoantibodies (autoAbs) in relation to disease severity and plasma cortisol response to physical exercise in patients with mild and moderate depression and healthy controls.

Methods

Physical exercise was used to elicit plasma cortisol response in 23 male patients with depression and 20 healthy controls and plasma samples were obtained before and after the exercise. Just before the exercise, patients and controls were evaluated by the Montgomery and Åsberg Depression Rating Scale (MADRS) and divided according to depression severity (14 mild and 9 moderate). Plasma levels of total and free VP- and OT-reactive IgG, IgA and IgM autoAbs were measured by ELISA and affinity of IgG and IgM autoAbs were measured by plasmon resonance technique at baseline before the exercise and analyzed with relation to the MADRS and cortisol response. Immunohistochemistry was used to evaluate autoAbs binding to the rat hypothalamus.

Results

Plasma levels of OT- and VP-reactive total IgG autoAbs were lower in patients with moderate depression vs. controls and patients with mild depression. Plasma levels of both OT- and VP-free IgG autoAbs were negatively correlated with MADRS scores. Affinity values of IgG and IgM autoAbs for both OT and VP displayed 100 fold variability among patients or controls but no significant group differences were found. Patients with moderate depression displayed blunted response of cortisol secretion to physical exercise. Baseline levels of VP total IgG and IgM autoAbs correlated negatively and VP-free IgG autoAbs correlated positively with plasma cortisol after physical exercise. Immunostaining of magnocellular hypothalamic neurons of the supraoptic and paraventricular nuclei by plasma IgG was present in 35% of the depression and in 14% of the controls groups, but this staining was not abolished by plasma preabsorption with OT or VP peptides.

Conclusion

These data show that changes of levels but not affinity of OT- and VP-reactive autoAbs can be associated with the altered mood in subjects with moderate depression and that levels of VP-reactive autoAbs are associated with cortisol secretion.     

HDACS抑制剂对人肝癌细胞株HepG2作用的研究

通过组蛋白去乙酰化酶（histone deacetylase,HDACS）抑制剂古抑菌素A（Trichostatin A,TSA）对人肝癌细胞株HepG2（以下简称HepG2）和正常肝细胞株L02（以下简称L02）增殖与凋亡作用的比较,探讨TSA对肝癌的作用机制。方法：应用光学显微镜、透射电镜、四氮唑蓝（MTT）法、脱氧核苷酸末端转移酶介导的dTP缺口末端标记技术（TUNEL法）、免疫细胞化学法观察经不同浓度TSA处理后的HepG2和L02的增殖、凋亡与凋亡相关蛋白的改变。结果：（1）HepG2细胞经TSA处理后,电镜下超微结构发生了凋亡早期改变。（2）小剂量TSA（250nmol／L）对HepG2细胞具有较强的生长抑制作用,对L02细胞影响不明显,当TSA浓度达到1000nmol／L以上时,对L02表现出明显的细胞毒性作用。（3）TSA可诱导HepG2细胞凋亡,并增加凋亡相关蛋白Bax的表达。结论：TSA可明显抑制肝癌细胞HepG2的增殖,其机制可能与上调Bax的表达,诱导细胞凋亡有关。     

Sialic acid: a novel marker of cardiovascular disease?

The global burden posed by cardiovascular disease (CVD), due to a rising incidence of known risk factors, underlines an urgent need to identify other potential risk factors. Sialic acid (SA), an abundant terminal monosaccharide of glycoconjugates, is a possible risk factor for CVD. Although large-scale epidemiological surveys have shown that serum total sialic acid (TSA) is positively associated with mortality from coronary artery disease (CAD) and stroke, studies investigating the correlation between serum TSA and the severity of atherosclerosis are conflicting. Clinical and epidemiological studies indicate that serum TSA is a marker of a sustained inflammatory response in CVD, rather than causal in nature. Data also indicates ethnic variation in baseline TSA. This article reviews current methods for determining serum TSA and evidence supporting serum TSA as a risk factor for CVD. Potential mechanisms for this role are examined. The use of serum TSA as a marker of atherosclerotic disease is evaluated.     

5-aza-dC和TSA对NIH/3T3细胞多能性基因表达作用的实验研究

目的本实验通过联合应用甲基转移酶抑制剂5-氮-2'-脱氧胞苷(5-aza-2'-deoxycytidine,5-aza-dC)和去乙酰化酶抑制剂曲古抑菌素A(Trichstatin A,TSA)对NIH/3T3胎鼠成纤维细胞进行DNA去甲基化重编程,以期使其表达与多向分化潜能性密切相关的基因。方法药物处理组与正常对照组NIH/3T3细胞的形态学观察。流式细胞技术检测药物处理前后NIH/3T3细胞的DNA甲基化水平。应用RT-PCR的方法检测多能性基因Oct4,Sox2,c-Myc和Klf4的表达情况。结果经过药物处理后的NIH/3T3细胞与对照组的细胞比较,从细胞形态来观察,没有明显的区别,均呈现成纤维细胞的外观。药物处理组的DNA甲基化水平较对照组明显降低。药物处理后细胞均呈现出Oct4,Sox2,c-Myc和Klf4基因的阳性表达。结论 5-aza-dC和TSA对NIH/3T3细胞进行表观重编程,可以使重编程后的体细胞中呈现与多向分化潜能基因的阳性表达。