IL-17A and TNF-α inhibitors induce multiple molecular changes in psoriasis.

Adalimumab and secukinumab are commonly used for moderate to severe psoriasis vulgaris (PV). Although distinct individual responses to and impaired effectiveness of these biological agents occur occasionally, little is known about the underlying reasons. Here, we report a proteomic analysis of psoriatic lesions from patients treated with these drugs using data-independent acquisition mass spectrometry (DIA-MS). Thousands of differentially expressed proteins (DEPs) changed over 12 weeks of treatment. Network analysis showed that DEPs could interact and induce transformation in matrix components, metabolic regulation, and immune response. The results of parallel reaction monitoring (PRM) analysis suggested that S100s, STAT1, KRT2, TYMP, SOD2, HSP90AB1, TFRC, and COL5A1 were the most significantly changed proteins in both groups. There was a positive association between the Psoriasis Area and Severity Index (PASI) score and three proteins (TFRC, IMPDH2, KRT2). Our study findings suggest that inhibition of IL-17A and TNF-α can induce changes in multiple molecules in psoriatic lesions and have an overlapping influence on the immune response and process through direct or indirect effects.

Melanocyte activation and skin barrier disruption induced in melasma patients after 1064 nm Nd:YAG laser treatment.

Melasma is a frequently acquired hyperpigmentary skin disorder, for which several therapies are available. Among them, 1064 nm QS Nd:YAG laser therapy is an effective method, but the recurrence rate of laser treatment is still high. The aim of the present study was to elucidate the mechanism of the high relapse rate of melasma after 1064 nm Nd:YAG laser treatment. Twenty-five female melasma patients were treated with 1064 nm Nd:YAG laser for 10 times. The lesional skin and non-lesional skin were evaluated by means of a reflectance confocal laser scanning microscope before and after laser treatment. Melanin content and transepidermal water loss (TEWL) were measured by an MPA9 skin multifunction tester accordingly. The melanin index value was significantly decreased in the lesional skin after laser treatment, while the non-lesional skin had no difference. The dendritic cells were observed at the level of the dermal-epidermal junction (DEJ) in the lesions of 8 patients before laser treatment, while after laser treatment, the dendritic cells were observed in all 25 subjects. Moreover, there was significant difference between the TEWL value of the lesions before and after laser treatment. Furthermore, the TEWL value was higher in lesions of the 8 subjects which had dendritic cells compared with other 17 subjects which had no dendritic cells, no matter before or after laser treatment. The relapse patients of melasma had higher TEWL value compared with the non-relapse patients. Melanocyte activation and skin barrier disruption may be related to the high relapse rate of melasma after laser treatment.

Up-regulation of TDAG51 is a dependent factor of LPS-induced RAW264.7 macrophages proliferation and cell cycle progression.

CONTEXT: As a component of the outer membrane in Gram-negative bacteria, lipopolysaccharide (LPS)-induced proliferation and cell cycle progression of monocytes/macrophages. It has been suggested that the proapoptotic T-cell death-associated gene 51 (TDAG51) might be associated with cell proliferation and cell cycle progression; however, its role in the interaction between LPS and macrophages remains unclear. OBJECTIVE: We attempted to elucidate the role(s) of TDAG51 played in the interaction between LPS and macrophages. MATERIALS AND METHODS: We investigated TDAG51 expression in RAW264.7 cells stimulated with LPS and examined the effects of RNA interference-mediated TDAG51 down-regulation. We used CCK-8 assay and flow cytometry analysis to evaluate the interaction between TDAG51 and LPS-induced proliferation and cell cycle progression in RAW264.7 cells. RESULTS: Our findings indicate that TDAG51 is up-regulated in LPS-stimulated RAW264.7 cells, the TDAG51 siRNA effectively reduced TDAG51 protein up-regulation following LPS stimulation in RAW264.7 cells, the significant changes of the proliferation and cell cycle progression of RAW264.7 cells in TDAG51 Knockdown RAW264.7 cells treated with LPS were observed. CONCLUSION: These findings suggested that TDAG51 up-regulation is a dependent event during LPS-mediated proliferation and cell cycle progression, and which increase our understanding of the interaction mechanism between LPS and macrophages.

Rapid Identification of Legionella Pathogenicity by Surface-Enhanced Raman Spectroscopy.

OBJECTIVE: To establish Surface-enhanced Raman Spectroscopy (SERS) can be used as a rapid and reliable method to distinguish virulent strain and mild strain of L. pneumophila. METHODS: Mortality data were collected from company departments through administrative documents, death certificates, etc. Trend analyses of cancer mortality were performed on the basis of 925 cancer deaths between 2001 and 2010. RESULTS: Our results indicated that the peaks of high virulence strains reached ⋝4000. This criterion was verified by subsequent cell experiments. In addition, we also conducted SERS rapid identification on the virulence of several collected clinical strains and obtained accurate results. CONCLUSION: The present study indicates that the established SERS protocol can be used as a rapid and reliable method to distinguish virulent and mildly virulent strains of L. pneumophila, which can be further used in clinical samples.

[Reconstitution of humoral immunity by the transplantation of human umbilical cord blood CD34+ cells into NOD/ SCID mice].

OBJECTIVE: To investigate the immune reconstitution by the transplantation of human umbilical cord blood CD34+ cells in the NOD/SCID mouse. METHODS: Mononuclear cells (MNC) were isolated from human fresh cord blood and CD34+ hematopoietic stem cells were selected by magnetic activated cell sorting method. The selected cells were transplanted via tail vein injection into 16 NOD/SCID mice after sublethal whole-body irradiation. Four mice were sacrificed respectively at 4th, 6th, 8th and 10th week after the transplantation, the harvested spleen and peripheral blood cells were used to cell phenotype analysis and humoral immune analysis, respectively. There were 14 mice in another two groups, 7 mice did not receive the transplantation after irradiation, 7 were used as blank control (no irradiation, no transplantation). RESULTS: The mice without transplantation all died within 2 weeks after irradiation. The survival rate of the mice with transplantation was 37.5% at 6th week after the irradiation, while the survival rate of blank control was 100%. At 4th, 6th, 8th and 10th week, the percentage of human CD45+ cells in transplantation group were 4.7 +/- 1.23, 9.22 +/- 2.07, 12.34 +/- 2.38, 8.14 +/- 2.36, respectively, and the percentage of CD19+ B lymphocytes were 1.07 +/- 0.50, 2.17 +/- 0.95, 3.34 +/- 0.90, 1.67 +/- 0.90, respectively. 10 weeks after the transplantation, human CD19+ B lymphocytes distribution were found in the transplanted mice spleen. CONCLUSION: The human-mouse chimeric immune model can be built in irradiated NOD/ SCID mice by the transplantation of human cord blood CD34+ cells. CD34+ cell differentiation declined with time, which might be due to the lack of appropriate cytokines.