Elderly atopic dermatitis: a new clinical subtype of atopic dermatitis? / 中华皮肤科杂志

Atopic dermatitis (AD) is a highly heterogeneous skin disease. In recent years, studies on precise classification of diseases has revealed a new subtype of AD--elderly AD. In the past, it was believed that AD mostly occurs in children. However, it has been found that the elderly are also a high-risk group of AD in recent years. Elderly AD is quite different from childhood and adult AD in terms of epidemiology, clinical manifestations, pathogenesis and treatment. Attention should be paid to the diagnosis, differential diagnosis and treatment of elderly AD.

Identification of Molecular Signatures in Mild Intrinsic Atopic Dermatitis by Bioinformatics Analysis

BACKGROUND: Atopic dermatitis (AD) is recognized as a common inflammatory skin disease and frequently occurred in Asian and Black individuals.OBJECTIVE: Since the limitation of dataset associated with human severe AD, this study aimed to screen potential novel biomarkers involved in mild AD.METHODS: Expression profile data (GSE75890) were obtained from the database of Gene Expression Omnibus. Using limma package, the differentially expressed genes (DEGs) between samples from AD and healthy control were selected. Furthermore, function analysis was conducted. Meanwhile, the protein-protein interaction (PPI) network and transcription factor (TF)-miRNA-target regulatory network were constructed. And quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate the expressions patterns of key genes.RESULTS: In total, 285 DEGs including 214 upregulated and 71 downregulated genes were identified between samples from two groups. The upregulated DEGs were mainly involved in nine pathways, such as hematopoietic cell lineage, pertussis, p53 signaling pathway, staphylococcus aureus infection, and cell cycle, while tight junction was the only pathway enriched by the downregulated DEGs. Cyclin B (CCNB)1, CCNB2, cyclin A (CCNA)2, C-X-C motif chemokine ligand (CXCL)10, and CXCL9 were key nodes in PPI network. The TF-miRNA-target gene regulatory network focused on miRNAs such as miR-106b, miR-106a, and miR-17, TFs such as nuclear factor kappa B subunit 1, RELA proto-oncogene, Sp1 transcription factor, and genes such as matrix metallopeptidase 9, peroxisome proliferator activated receptor gamma , and serpin family E member 1. Moreover, the upregulation of these genes, including CCNB1, CCNB2, CCNA2, CXCL10, and CXCL9 were confirmed by qRT-PCR.CONCLUSION: CCNB1, CCNB2, CCNA2, and CXCL9 might be novel markers of mild AD. miR-106b and miR-17 may involve in regulation of immune response in AD patients.

Effect of tacrolimus on the expression and function of protease-activated receptor 2 in human keratinocytes / 中华皮肤科杂志

Objective@#To evaluate the in vitro effect of tacrolimus on the expression and function of protease-activated receptor 2 (PAR-2) in cultured human keratinocytes.@*Methods@#After 24-hour co-culture of human keratinocytes with 10-9 - 10-5 mol/L tacrolimus, semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) was performed to determine the mRNA expression of PAR-2, immunofluorescence (IF) staining and Western blot analysis were performed to determine the protein expression of PAR-2 in the keratinocytes, and the fluorescent calcium probe fluo-4 was used to evaluate the effect of tacrolimus at different concentrations on the intracellular calcium concentration after the activation of PAR-2 in the keratinocytes. The group treated without tacrolimus served as control group. One-way analysis of variance was used to compare the PAR-2 expression and calcium concentration in the human keratinocytes in different groups, and least significant difference (LSD) -t test was carried out for multiple comparisons.@*Results@#PAR-2 was expressed on both the membrane and cytoplasm of keratinocytes. After 24-hour co-culture of keratinocytes with 10-9 - 10-5 mol/L tacrolimus, the PAR-2 mRNA expression significantly decreased in these cells compared with the control group (all P < 0.05) , and was negatively correlated with the tacrolimus concentration (r=-0.962, P = 0.009) . IF staining and Western blot analysis showed that the PAR-2 protein expression was significantly lower in the 10-5- and 10-6-mol/L tacrolimus groups than in the control group (both P < 0.05) , and decreased to a certain extent in the 10-7-mol/L tacrolimus group (IF staining: P < 0.05; Western blot analysis: P > 0.05) . No significant difference in the PAR-2 protein expression was observed between the 10-8- or 10-9-mol/L tacrolimus group and the control group (both P > 0.05) . After 24-hour co-culture, the peak concentration of intracellular calcium after PAR-2 activation was significantly lower in the 10-5-, 10-6- and 10-7-mol/L tacrolimus groups (peak absorbance: 1 463 ± 283, 1 455 ± 270, 1 423 ± 291 respectively) than in the control group (1 602 ± 407; t = 2.582, 2.821, 2.923, P = 0.032, 0.022, 0.019, respectively) , while there was no significant difference between the 10-8- or 10-9-mol/L tacrolimus group (1 649 ± 379, 1 633 ± 415 respectively) and the control group (t = 0.846, 0.462, P = 0.422, 0.657, respectively) .@*Conclusion@#Tacrolimus can inhibit PAR-2 expression and suppress calcium mobilization induced by a PAR-2 agonist in keratinocytes.

Effect of tacrolimus on the expression and function of protease-activated receptor 2 in human keratinocytes / 中华皮肤科杂志

Objective To evaluate the in vitro effect of tacrolimus on the expression and function of protease-activated receptor 2(PAR-2)in cultured human keratinocytes. Methods After 24-hour co-culture of human keratinocytes with 10-9-10-5 mol/L tacrolimus, semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR)was performed to determine the mRNA expression of PAR-2, immunofluorescence(IF)staining and Western blot analysis were performed to determine the protein expression of PAR-2 in the keratinocytes, and the fluorescent calcium probe fluo-4 was used to evaluate the effect of tacrolimus at different concentrations on the intracellular calcium concentration after the activation of PAR-2 in the keratinocytes. The group treated without tacrolimus served as control group. One-way analysis of variance was used to compare the PAR-2 expression and calcium concentration in the human keratinocytes in different groups, and least significant difference(LSD)-t test was carried out for multiple comparisons. Results PAR-2 was expressed on both the membrane and cytoplasm of keratinocytes. After 24-hour co-culture of keratinocytes with 10 - 9- 10 - 5 mol/L tacrolimus, the PAR-2 mRNA expression significantly decreased in these cells compared with the control group(all P < 0.05), and was negatively correlated with the tacrolimus concentration(r=-0.962, P=0.009). IF staining and Western blot analysis showed that the PAR-2 protein expression was significantly lower in the 10-5- and 10-6-mol/L tacrolimus groups than in the control group (both P < 0.05), and decreased to a certain extent in the 10-7-mol/L tacrolimus group(IF staining:P<0.05;Western blot analysis:P>0.05). No significant difference in thePAR-2 protein expression was observed between the 10-8-or 10-9-mol/L tacrolimus group and the control group(both P>0.05). After 24-hour co-culture, the peak concentration of intracellular calcium after PAR-2 activation was significantly lower in the 10-5-, 10-6- and 10-7-mol/L tacrolimus groups (peak absorbance:1463 ± 283, 1455 ± 270, 1423 ± 291 respectively)than in the control group(1602 ± 407;t=2.582, 2.821, 2.923, P=0.032, 0.022, 0.019, respectively), while there was no significant difference between the 10-8-or 10-9-mol/L tacrolimus group(1649 ± 379, 1633 ± 415 respectively)and the control group(t=0.846, 0.462, P=0.422, 0.657, respectively). Conclusion Tacrolimus can inhibit PAR-2 expression and suppress calcium mobilization induced by a PAR-2 agonist in keratinocytes.

A twin study of genetic and environmental influences on relationship between attention deficit and anxiety/depression in children and adolescents / 中华流行病学杂志

Objective To understand the genetic and environmental influences on the relationship between attention deficit and anxiety/depression in children and adolescents.Methods A total of 1 062 same-sex twins aged 6-18 years were included in this study.A parent-rated child behavior checklist (CBCL) was used in the assessment.Software Mx was used to fit the univariate model of structural equation.The relationship between attention deficit and anxiety/depression was analyzed through bivariate genetic modeling.Results The genetic factor had influence on the relationship between attention deficit and anxiety/depression (rg=0.48).Shared and non-shared environmental correlation scores of attention deficit and anxiety/depression were 0.86 and 0.14 respectively.Conclusion Common genetic and shared environmental influences can explain the relationship between attention deficit and anxiety/depression in children and adolescents.

A twin study of genetic and environmental influences on relationship between attention deficit and anxiety/depression in children and adolescents / 中华流行病学杂志

Objective To understand the genetic and environmental influences on the relationship between attention deficit and anxiety/depression in children and adolescents.Methods A total of 1 062 same-sex twins aged 6-18 years were included in this study.A parent-rated child behavior checklist (CBCL) was used in the assessment.Software Mx was used to fit the univariate model of structural equation.The relationship between attention deficit and anxiety/depression was analyzed through bivariate genetic modeling.Results The genetic factor had influence on the relationship between attention deficit and anxiety/depression (rg=0.48).Shared and non-shared environmental correlation scores of attention deficit and anxiety/depression were 0.86 and 0.14 respectively.Conclusion Common genetic and shared environmental influences can explain the relationship between attention deficit and anxiety/depression in children and adolescents.

Effect of estrogen, hydralazine and ultraviolet ray on DNA methyltransferase-1 activity in patients with systemic lupus erythematosus / 中华皮肤科杂志

Objective To explore the mechanism underlying the induction of systemic lupus erythematosus (SLE) by estrogen, hydralazine and ultraviolet irradiation. Methods Peripheral blood mononuclear cells (PBMCs) were harvested from 10 patients with SLE and 9 normal human controls, and cultured with or without the intervention with estrogen, hydralazine or ultraviolet irradiation. The DNA methyltransferase-1 (DNMT1) activity of PBMCs was quantified by using DNMT activity/inhibition assay kit. Results No statistical difference was observed in DNMT1 activity between patients with SLE and normal controls (0.36 ± 0.24 vs 0.46 ± 0.17, P ＞ 0.05). A significant decrease was noted in DNMT1 activity in PBMCs from patients with SLE after intervention with estrogen (0.32 ± 0.18 vs 0.46 ± 0.17, t = 1.725, P ＜ 0.05), hydralazine (0.33 ±0.13 vs 0.46 ± 0.17, t = 1.739, P ＜ 0.05) and ultraviolet irradiation (0.30 ± 0.14 vs 0.46 ± 0.17, t = 1.739,P ＜ 0.05 ) compared with that from normal human controls. The treatment with hydralazine also induced an attenuation of DNMT1 activity in PBMCs from normal human controls (0.38 ± 0.12 vs 0.46 ± 0.17, P＜ 0.05).Conclusion Estrogen, hydralazine and ultraviolet irradiation can inhibit the DNMT1 activity of SLE patients,indicating that they may induce the initiation of SLE by altering the activity of DNMT1.