Background: Excessive growth of keratinocytes is the critical event in the etiology of psoriasis.However, the underlying molecular mechanism of psoriatic keratinocyte hyperproliferation is still unclear. Objective: This study aimed to figure out the potential contributory role of S-phase kinase-associated protein 2 (SKP2) in promoting the hyperproliferation of keratinocytes in psoriasis. Methods: We analyzed microarray data (GSE41662) to investigate the gene expression of SKP2in psoriatic lesion skins compared with their adjacent non-lesional skin. Then, we further confirmed the mRNA and protein expression of SKP2 in human psoriatic skin tissues, imiquimod (IMQ)-induced psoriatic mice back skins and tumor necrosis factor α (TNF-α), interleukin (IL)-17A and IL-6-stimulated keratinocytes by using real-time quantitative polymerase chain reaction and western blot (WB). Furthermore, we explored the potential pathogenic role and its underlying cellular mechanism of SKP2 in promoting keratinocytes hyperproliferation through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, cell cycle detection, 5-ethynyl-2′-deoxyuridine staining and WB. Finally, we determined whether inhibition of SKP2 can effectively alleviate the keratinocytes hyperproliferation in vivo. Results: We identified that SKP2 is aberrantly upregulated in the psoriatic lesion skin and cytokines-stimulated keratinocytes. Moreover, upregulated SKP2 augments cytokines-induced keratinocytes hyperproliferation. Mechanistically, enhanced SKP2 increased the S phase ratio through inhibiting Cyclin-Dependent Kinase Inhibitor p27 (P27 Kip1) expression. Correspondingly, suppression of SKP2 with SMIP004 can significantly ease the epidermis hyperplasia in vivo. Conclusion Our results suggest that elevated SKP2 can empower keratinocytes proliferation and psoriasis-like epidermis hyperplasia via downregulation of P27 Kip1. Therefore, targeting SKP2-P27 Kip1 axis might be a promising therapeutic strategy for the treatment of psoriasis in future.

Objective To explore the value of prostate specific antigen density (PSAD) in clinical decision making for patients with prostate imaging reporting and data system version 2 (PI-RADS v2) category 3 lesions.Methods Totally 54 patients with PI-RADS v2 category 3 lesions who underwent prostate biopsy before MRI were enrolled and divided into prostate cancer (PCa) group (n=11) and benign group (n=43) according to biopsy results.Then clinical data and imaging features,including total prostate specific antigen (TPSA),free prostate specific antigen (FPSA),FPSA/TPSA ratio (F/T),PSAD,prostate volume and the volume of index lesion were collected and statistically analyzed between the two groups.ROC curve was used to evaluate the diagnostic efficacy of PSAD in predicting malignant and benign lesions in patients with PI RADS v2 category 3 lesions.Results PSAD had statistical difference (P=0.006),whereas TPSA,FPSA,F/T,prostate volume and the volume of index lesion showed no statistical differences between PCa group and benign group (all P＞0.05).ROC curves showed that area under the curve was 0.771(P＜0.05).Using the optimal threshold of PSAD-0.25 ng/ml2,the sensitivity and specificity of PSAD in predicting PCa and benign lesions was 72.73 ％ (8/11) and 74.42％(32/43),respectively.Conclusion PSAD is an effective index to predict the risk of PCa in patients with PI-RADS v2 category 3 lesions.Using the threshold of PSAD=0.25 ng/ml2 to screen high risk patients for prostate biopsy,the positive rate could be improved and unnecessary biopsies could be avoided.

Breast Neoplasms ; genetics ; Carcinoma ; genetics ; Female ; Gene Amplification ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Polymerase Chain Reaction ; methods ; Receptor, ErbB-2 ; genetics

AIM: To investigate the effect of detoxifying herbs polygonum cuspidatum, and hawthorn, herb of promoting blood flow, on pathologic morphology and inflammatory factors in apolipoprotein E gene knockout mice, in order to approach the possible regulatory mechanism of polygonum cuspidatum and hawthorn for treating artherosclerosis (AS) unstable plaque. METHODS: The animals were divided into 7 groups (12 mice in every group). The ApoE (-/-) mice fed with high fat diet were divided into polygonum cuspidatum group, hawthorn group, polygonum cuspidatum + hawthorn group, Xuezhikang group and high fat diet model group. Moreover, ApoE (-/-) mice fed with normal diet (normal diet group) and C57BL/6J mice fed with normal diet (normal control group) were set up. After intragastric administration for 17 weeks, serum hs-CRP was detected, aorta structure was observed under light microscope and NF-κB protein expression was determined by immunohistochemistry. RESULTS: The pathological change of AS in aorta in all groups fed with high fat diet and normal diet group were observed with different degree. The changes of aortic lesion in all treatment groups were reduced. The levels of NF-κB and hs-CRP in high fat diet group were significant higher than those in normal control group and normal diet group. Serum NF-κB and hs-CRP levels decreased in every treatment group, which were significant different from those in high fat diet model group (P<0.01). Among them, the changes in polygonum cuspidatum and hawthorn groups were the best. CONCLUSION: Chinese herbs of polygonum cuspidatum and hawthorn reduce inflammatory factors NF-κB and hs-CRP expression and play a role in anti-AS formation.

AIM: In this paper, we studied the efficiencies and the mechanisms of a new Chinese herb Qcimum basilicum polysaccharide (BP) on PG cell metastasis in vitro. METHODS: The number of tumor cells going through matrigel was assayed and used to represent the ability of the invasion and migration of PG cells. Using Scrape-loading and dye transfer (SLDT) technique, the efficiencies of BP on recovering PG cell gap junction -mediated intercellular communication (GJIC) was measured. The expressions of c-myc, nm23-H1 and Tiam-1 genes mRNA in PG cells treated with BP were determined by RT-PCR. RESULTS: Compared with the control, the action of invasion and migration of PG cells were decreased after treated with BP (P

AIM: To investigate the mechanism of basil polysaccharide in inhibiting the invasion and metastasis ability of ovarian cancer,and to evaluate the potency of hypoxia tumour microenvironment in affecting the action of basil polysaccharide.METHODS: The human ovarian cancer cell line SKOV3 was cultured with basil polysaccharide under normoxia(21% O2,5% CO2) and hypoxia(1% O2,5% CO2,94% N2),respectively.Morphology of this cell line in different groups under different oxygen concentrations was observed under inverted phase contrast microscope.The cell invasiveness was tested by transwell method and the activities of matrix metalloproteinase-2(MMP-2) among each group were analyzed by gelatin zymography.The expressions of OPN mRNA and protein levels were detected by RT-PCR and immunohistochemistry,respectively.RESULTS: Compared to the control group,basil polysaccharide decreased the invasiveness and migrating ability and inhibited the secretion of MMP-2 in SKOV3 cells.Basil polysaccharide also reduced the expression level of osteopontin(transcriptional level and protein level) of the SKOV3 cells in both normoxic and hypoxic conditions.Moreover,these functions of basil polysaccharide were more obviously in hypoxia.CONCLUSION: The migrating ability of the SKOV3 cells is enhanced under hypoxic condition.Basil polysaccharide may inhibit the invasiveness and migrating ability of SKOV3 cells through reducing osteopontin expression and MMP-2 secretion.