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Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) are severe cutaneous adverse drug reactions, rare but life-threatening, characterized by massive keratinocyte death and development of a systemic inflammatory response. Pyroptosis is a lytic form of pro-inflammatory programmed necrotic cell death which participates in the pathogenesis of various inflammatory diseases, it depends on activation of inflammasomes such as NLRP3/NALP1/AIM2/NLRC4 and inflammatory caspases (caspase 1/4/5), subsequently it is executed by pore-forming protein of the gasdermin family, resulting in releases of inflammatory cytokines such as IL-1β, IL-18. However, does pyroptotic machinery exist in the SJS/TEN remains open. In our study, we present evidence for the involvement and mechanism of pyroptosis in SJS/TEN keratinocytes. Inflammatory cytokines TNF-α and IFN-γ participating in keratinocyte pyroptosis through strengthening of cytoplasmic dsDNA/AIM2/Caspase-1/GSDMD pathway were identified in vivo and in vitro. Further, we observed that all of the four small molecular pyroptosis inhibitors including Z-YVAD-FMK，dimethyl fumarate (DMF), necrosulfonamide (NSA) and disulfiram caused a significant inhibition of pyroptosis in human primary keratinocytes, and significantly downregulated the release of pyroptosis-related inflammatory cytokines IL-1β and IL-18. These discoveries expand our understanding of the pathogenesis of SJS/TEN and it is hoped that this could facilitate the development of new therapeutics for the treatment of SJS/TEN patients with activated pyroptosis in keratinocytes.

A new ceramide urticamide (1), two new secolignans urticalactones I (2) and Ⅱ (3), and a new flavonoid glycoside urticaside (4), together with 15 known compounds (4-19), were isolated from the leaves of Urtica fissa, a folk medicine for rheumatism arthritis in China. The active evaluation results showed that 1, 2, 3, 8, and 13 possessed the potent anti-inflammatory. They could inhibit the release of NO and TNF-α in lipopolysaccharide (LPS) stimulated RAW 264.7 cells, with IC50 values less than 4.0 μM.

Several twin studies have investigated the overlap between attention deficit hyperactivity disorder (ADHD) and externalizing problems; however, limited information is known regarding the genetic and environmental contribution to the overlap between ADHD and internalizing problems. This study examined the genetic and environmental influences on the variation in and covariation between ADHD symptoms and internalizing problems by using the Child Behavior Checklist (CBCL). We investigated 1,316 child and adolescent twins, including 780 monozygotic twins and 536 dizygotic twins, aged 6 years to 18 years from the Chinese Child and Adolescent Twin Registry. ADHD symptoms and internalizing problems were quantified through parent rating by using the Attention Problems Scale and other three scales, which include Anxious/Depressed, Withdrawn, and Somatic Complaints of CBCL. Genetic and environmental susceptibilities common to ADHD symptoms and internalizing problems were examined through bivariate twin modeling. Results showed that genetic factors substantially influenced the ADHD symptoms with a heritability of 72%. Modest genetic influences and substantial shared environmental influences (20-77%) were observed in the three internalizing problem scales. Common genetic and shared environmental influences were essential for the overlap between ADHD and the three internalizing problems respectively. Approximately one-fifth of the genetic variance of ADHD symptoms was shared with anxiety/depression. In conclusion, substantial genetic and shared environmental influences on ADHD symptoms and internalizing problems were observed in Chinese children and adolescents. Our finding supports a common etiology between ADHD and internalizing problems. This finding can also help explain the co-existence of these behavior problems. © 2015 Wiley Periodicals, Inc.

The adsorption process of Cr (VI) in aqueous solution on activated carbon prepared by discarded disposable chopsticks was investigated to study the effect factors on adsorption properties. adsorption mechanism was discussed. The results showed that the adsorption performance was influenced by partical size, dosage, pH of medium, initial concentration and adsorption time. Adsorption reached equilibrium after 60min at temperature 25°C, pH=3, 80 mesh of adsorbent particle size. The highest removal efficiency can reach 92%. The results indicated that activated carbon as adsorbent can effectively deal with waste water containing (VI).

Extramammary Paget’s disease (EMPD) is a rare cutaneous malignancy accounting for approximately 1-2% of vulvar cancers. The rarity of this disease has caused difficulties in characterization and the molecular mechanism underlying EMPD development remains largely unclear. Here we used microarray analysis to identify differentially expressed genes in EMPD of the scrotum comparing with normal epithelium from healthy donors. Agilent single-channel microarray was used to compare the gene expression between 6 EMPD specimens and 6 normal scrotum epithelium samples. A total of 799 up-regulated genes and 723 down-regulated genes were identified in EMPD tissues. Real-time PCR was conducted to verify the differential expression of some representative genes, including ERBB4, TCF3, PAPSS2, PIK3R3, PRLR, SULT1A1, TCF7L1, and CREB3L4. Generally, the real-time PCR results were consistent with microarray data, and the expression of ERBB4, PRLR, TCF3, PIK3R3, SULT1A1, and TCF7L1 was significantly overexpressed in EMPD (P

It seems that global DNA hypomethylation in CD4+T cells is linked to the pathogenesis of systemic lupus erythematosus (SLE). However, the underlying mechanism by which SLE patients show hypomethylated DNA remains unclear. This study explored the relationship between DNA methylation patterns and expression levels of DNA methyltransferases (DNMT1) and MBD2 in CD4+T cells of SLE patients.CD4+T cells were obtained from 30 patients with SLE and 18 normal controls. The global DNA methylation levels in CD4+T cells were evaluated by the Methyflash DNA methylation quantification kit. The mRNA levels of DNMT1 and MBD2 were quantified by quantitative real-time polymerase chain reaction.SLE patients had significantly lower global DNA methylation levels than controls, and the global DNA methylation was inversely correlated with the SLE disease activity index (SLEDAI). The mRNA levels of DNMT1 in SLE patients were significantly lower than that of controls and there was no correlation between DNMT1 mRNA levels and SLEDAI but there was a positive correlation between DNMT1 mRNA levels and global DNA methylation. The mRNA levels of MBD2 in SLE patients were significantly higher than in controls, and there was positive correlation between MBD2 mRNA levels and SLEDAI and an inverse correlation between MBD2 mRNA levels and global DNA methylation.Global DNA hypomethylation may play a pivotal role in the pathogenesis of SLE. Abnormal expression levels of DNMT1 and MBD2 mRNA may be important causes of the global hypomethylation observed in CD4+T cells in SLE.

To explore the expression of Toll-like receptor 4 (TLR4) in brain tissue of chronic Toxoplasma infection rats and its effect on brain injury.Ten male SD rats were randomly divided into 2 groups, namely control and infection groups. Each rat in the infection group was intraperitoneal injected with Toxoplasma gondii tachyzoites 10(7)/ml x 2 ml, and that in the control group was injected with 2 ml sterile normal sodium. After 10 weeks, the expression of TLR4 mRNA in the brain was determined by RT-PCR, and the levels of IL-1beta and IL-4 in peripheral blood sera were detected by ELISA.Compared with the control group, the expression of TLR4 gene and the peripheral blood serum level of IL-1beta of rats in the Toxoplasma gondii infection group were both significantly increased, with all P values were less than 0.05, and the level of IL-4 was also increased, but the difference had no statistically significance (P0.05).TLR4 might be involved in inflammatory reactions of brain injury for chronic Toxoplasma gondii infection rats.