Relationship between rosacea and sleep

Rosacea is a chronic facial skin disease involved in neurovascular dysregulation and neurogenic inflammation. Behavioral factors such as stress, anxiety, depression and sleep were identified to be associated with other inflammatory skin diseases. Few studies have reported sleep status in rosacea. Aiming to investigate the relationship between rosacea and sleep, a case–control survey was conducted, enrolling 608 rosacea patients and 608 sex- and age-matched healthy controls. Sleep quality was assessed through the Pittsburgh Sleep Quality Index (PSQI) questionnaire. Diagnosis and severity grading of rosacea were evaluated under the standard guidelines of the National Rosacea Society. More rosacea patients (52.3%, n = 318) suffered poor sleep quality (PSQI, >5) than the healthy controls (24.0%, n = 146), displaying a much higher PSQI score (rosacea vs control, 6.20 vs 3.95). There was a strong association between sleep quality and rosacea (odds ratio [OR], 3.525; 95% confidence interval [CI], 2.759–4.519). Moreover, the severity of rosacea was also associated with sleep quality (OR, 1.847; 95% CI, 1.332–2.570). Single nucleotide polymorphisms in hydroxytryptamine receptor 2A and adrenoceptor-β1 genes, which are associated with sleep behaviour, were detected and revealed to be associated with rosacea. Furthermore, the LL-37-induced rosacea-like phenotype and sleep-deprivation mice models were applied, revealing that sleep deprivation aggravated the rosacea-like phenotype in mice, with higher expression of matrix metallopeptidase 9, Toll-like receptor 2, cathelicidin antimicrobial peptide and vascular endothelial growth factor. In conclusion, rosacea patients presented poorer sleep quality, as well as a higher propability of genetic background with sleep disturbance. In addition, poor sleep might aggravate rosacea through regulating inflammatory factors, contributing to a vicious cycle in the progression of disease.     

Kynurenine pathway is altered in BDNF Val66Met knock-in mice: Effect of physical exercise

The Brain-Derived Neurotrophic Factor (BDNF) Val66Met polymorphism has been correlated with increased predisposition to develop cognitive and psychiatric disorders, and with a reduced response to some therapeutic treatments. However, the mechanisms underlying these impairments are currently not completely understood. Remarkably, kynurenine pathway alterations have also been implicated in cognitive and psychiatric disorders. Moreover, recent evidence suggests that physical exercise may promote beneficial effects by controlling kynurenine metabolism in the muscle.The aim of the present study was to assess whether the kynurenine pathway was differentially regulated in sedentary and exercising wild-type (BDNF^Val/Val) and homozygous knock-in BDNF Val66Met (BDNF^Met/Met) mice. We found that plasma and hippocampal levels of kynurenic acid and the hippocampal mRNA levels of IDO1 and KAT2 protein levels were increased in BDNF^Met/Met mice and were not modulated by physical exercise. On the contrary, KAT1 protein levels in the gastrocnemius muscle were reduced, whereas MCP1 mRNA in the gastrocnemius muscle and GFAP protein in the hippocampus were increased in BDNF^Met/Met mice compared to BDNF^Val/Val mice, and reduced by physical exercise. Physical exercise increased plasmatic kynurenine levels only in BDNF^Met/Met mice, and protein levels of KAT1 and KAT4 in the gastrocnemius muscle and hippocampus respectively, regardless of the genotype. Finally, we found that physical exercise was able to enhance the hippocampal-dependent memory only in the BDNF^Val/Val mice. Overall our results showing an overactivation of the kynurenine pathway in the BDNF^Met/Met mice may suggest a possible mechanism underlying the cognitive deficits reported in the BDNF Val66Met carriers.     

复发性口腔溃疡免疫细胞的效应

复发性口腔溃疡是口腔科常见多发性疾病,与多种因素导致的自体免疫失衡有关。表现为免疫细胞活性和数量上的改变,特别是高表达或不正常表达CD4+、 CD8+细胞以及 CD4+/ CD8+的改变,并伴有多种细胞因子的变化,包括 IL-2 、IL-6、IL-8﹑IL-10、INF-γ 和TNF-α等多种细胞因子的异常表达以及相关细胞因子的基因突变导致的基因多态性。T淋巴细胞介导的细胞免疫在复发性口腔溃疡疾病的发生、发展过程中起重要作用。     

RNF213基因相关脑血管病研究进展

颅内大动脉狭窄/闭塞(intracranial major artery stenosis/occlusion,ICASO)是我国缺血性卒中最常见病因之一。既往研究提示其与烟雾病在受累血管分布、种族差异性等方面具有相似性。环指蛋白213(ring finger protein 213,RNF213)基因是烟雾病的易感基因。研究发现该基因与ICASO、大动脉粥样硬化性缺血性卒中、颅内动脉瘤同样具有相关性,提示RNF213基因可能与脑血管病发生、发展存在密切的联系。本文旨在通过回顾国内外相关文献,就RNF213结构、功能、基因多态性及与脑血管病相关性等问题进行概述。     

中国肾移植患者红细胞内嘌呤类药物活性代谢物6-硫鸟嘌呤核苷酸浓度监测及影响因素分析

目的：研究服用硫唑嘌呤（AZA）中国肾移植患者红细胞（RBC）内活性代谢物6-硫鸟嘌呤核苷酸（6-TGNs）分布特征及影响因素，为临床合理应用嘌呤类药物提供依据。方法：以89例中国肾移植患者为研究对象，关联分析年龄、性别、体质量、AZA剂量和TPMT活性对RBC内6-TGNs浓度的影响，并应用SPSS v20.0软件进行多元线性回归分析。结果：89例中国肾移植患者RBC内6-TGNs浓度呈非正态分布（P<0.000 1），6-TGNs浓度中位数为167.60（四分位间距，108.10~300.80） pmol/8×10⁸ RBC，个体间差异约24.3倍。关联分析显示患者年龄、性别、体质量、TPMT活性对6-TGNs浓度均无显著影响（P>0.05）；而AZA剂量与6-TGNs浓度间呈显著正相关性（r_s=0.307 1，P<0.01）。多元线性回归分析显示，RBC内6-TGNs浓度与AZA剂量间呈显著正相关（P<0.001），与TPMT活性呈显著负相关（P<0.05）。结论：AZA剂量和RBC内TPMT活性协同影响嘌呤类药物活性代谢物6-TGNs浓度，进而影响该类药物临床疗效和毒性反应。     

Genetic variants of the peroxisome proliferator-activated receptor (PPAR) signaling pathway genes and risk of pancreatic cancer

Because the peroxisome proliferator-activated receptor (PPAR) signaling pathway is involved in development and progression of pancreatic cancer, we investigated associations between genetic variants of the PPAR pathway genes and pancreatic cancer risk by using three published genome-wide association study datasets including 8477 cases and 6946 controls of European ancestry. Expression quantitative trait loci (eQTL) analysis was also performed for correlations between genotypes of the identified genetic variants and messenger RNA (mRNA) expression levels of their genes by using available databases of the 1000 Genomes, TCGA, and GTEx projects. In the single-locus logistic regression analysis, we identified 1141 out of 17 532 significant single-nucleotide polymorphisms (SNPs) in 112 PPAR pathway genes. Further multivariate logistic regression analysis identified three independent, potentially functional loci (rs12947620 in MED1, rs11079651 in PRKCA, and rs34367566 in PRKCB) for pancreatic cancer risk (odds ratio [OR] = 1.11, 95% confidence interval [CI], [1.06-1.17], P = 5.46 × 10⁻⁵; OR = 1.10, 95% CI, [1.04-1.15], P = 1.99 × 10⁻⁴; and OR = 1.09, 95% CI, [1.04-1.14], P = 3.16 × 10⁻⁴, respectively) among 65 SNPs that passed multiple comparison correction by false discovery rate (< 0.2). When risk genotypes of these three SNPs were combined, carriers with 2 to 3 unfavorable genotypes (NUGs) had a higher risk of pancreatic cancer than those with 0 to 1 NUGs. The eQTL analysis showed that rs34367566 A>AG was associated with decreased expression levels of PRKCB mRNA in 373 lymphoblastoid cell lines. Our findings indicate that genetic variants of the PPAR pathway genes, particularly MED1, PRKCA, and PRKCB, may contribute to susceptibility to pancreatic cancer.