PromotionLens: Inspecting Promotion Strategies of Online E-commerce via Visual Analytics.

Promotions are commonly used by e-commerce merchants to boost sales. The efficacy of different promotion strategies can help sellers adapt their offering to customer demand in order to survive and thrive. Current approaches to designing promotion strategies are either based on econometrics, which may not scale to large amounts of sales data, or are spontaneous and provide little explanation of sales volume. Moreover, accurately measuring the effects of promotion designs and making bootstrappable adjustments accordingly remains a challenge due to the incompleteness and complexity of the information describing promotion strategies and their market environments. We present PromotionLens, a visual analytics system for exploring, comparing, and modeling the impact of various promotion strategies. Our approach combines representative multivariant time-series forecasting models and well-designed visualizations to demonstrate and explain the impact of sales and promotional factors, and to support "what-if" analysis of promotions. Two case studies, expert feedback, and a qualitative user study demonstrate the efficacy of PromotionLens.

Wnt/ß-Catenin and Wnt5a/Ca Pathways Regulate Proliferation and Apoptosis of Keratinocytes in Psoriasis Lesions.

BACKGROUND / AIMS: Wnt5a is overexpressed in psoriasis lesions, however the mechanism by which Wnt5a is involved in the pathogenesis of psoriasis is not clear. To address this, the expression of Wnt5a in psoriatic lesions and its effect on keratinocyte cell proliferation and apoptosis was examined in vitro. METHODS: The expression levels of WNT5A, and genes encoding its receptors frizzled2 (FZD2) and frizzled5 (FZD5) were examined in samples obtained from individuals with psoriasis and healthy controls. Knockdown of Wnt5a with short interfering (si)RNAs was performed in cultured HaCaT keratinocytes and normal human keratinocytes (NHK), and the expression of Wnt5a, protein kinase C (PKC), and ß-catenin were determined, and cell cycle activity, proliferation and apoptosis were assessed. RESULTS: The expression of WNT5A, FZD2 and FZD5 mRNA and protein were increased in psoriatic lesions. Wnt5a knockdown suppressed proliferation and induced apoptosis in HaCaT and NHK cells. Additionally, expression of PCNA, MKI67, CCND1, BCL2, CTNNB1, and genes encoding PKC and survivin were downregulated, whereas CASP3 was upregulated. The mRNA levels of the Wnt pathway inhibitors DKK1 and SFRP1 were upregulated, Western blotting analyses demonstrated reduction in ß-catenin and PKC protein levels. CONCLUSION: Knockdown of Wnt5a suppresses the proliferation of keratinocytes and induces apoptosis by inhibiting the Wnt/ß-catenin or Wnt5a/Ca(2+) pathways.

IL-10 gene polymorphisms and susceptibility to systemic lupus erythematosus: a meta-analysis.

BACKGROUND: A number of observational studies have been conducted to investigate the association of the IL-10 gene polymorphisms with systemic lupus erythematosus (SLE) susceptibility. However, their results are conflicting. METHOD: We searched published case-control studies on the IL-10 polymorphisms and SLE in PubMed, EMBASE and Chinese Biomedical Literature Database. A meta-analysis was conducted using a fixed-effect or random-effect model based on between-study heterogeneity. RESULTS: A total of 42 studies with 7948 cases and 11866 controls were included in this meta-analysis. Among Caucasians, the CA27 allele of the IL10.G microsatellites (OR 2.38, 95% CI 1.01-5.62), the G allele of the IL-10 -1082G/A polymorphism (G vs. A: OR 1.21, 95% CI 1.02-1.44; GG vs. AA: OR 1.45, 95% CI 1.16-1.82; GG+GA vs. AA: OR 1.16, 95% CI 1.03-1.29) and its associated haplotype -1082G/-819C/-592C (OR 1.25, 95% CI 1.10-1.42) were associated with increased SLE susceptibility without or with unimportant between-study heterogeneity. Removing studies deviating from Hardy-Weinberg equilibrium (HWE) hardly changed these results. Among Asians, the CA21 allele of the IL-10.G microsatellites (OR 1.28, 95% CI 1.02-1.60) and the -1082G/-819C/-592C haplotype (OR 1.24, 95% CI 1.00-1.53) were associated with increased SLE susceptibility, but with substantial between-study heterogeneity or sensitive to HWE status. Removing studies deviating from HWE also produced statistically significant associations of the IL-10 -1082G/A (GG vs. AA: OR 3.21, 95% CI 1.24-8.28; GG vs. AA+GA: OR 2.85, 95% CI 1.19-6.79) and -592C/A polymorphisms (CC+CA vs. AA: OR 0.69, 95% CI 0.51-0.94) with SLE among Asians. CONCLUSION: This meta-analysis showed that the IL10.G microsatellites, the IL-10 -1082G/A and -592C/A polymorphisms and the haplotype -1082G/-819C/-592C are associated with SLE susceptibility. Besides, this is the first time to report an association between the CA27 allele of the IL-10.G microsatellites and SLE among Caucasians. Further studies are needed to confirm these findings.

MiR-155 negatively regulates c-Jun expression at the post-transcriptional level in human dermal fibroblasts in vitro: implications in UVA irradiation-induced photoaging.

OBJECTIVE: C-Jun plays a critical role in ultraviolet A (UVA) irradiation-induced photoaging. The exact mechanisms by which UVA irradiation up-regulates c-Jun expression in human dermal fibroblasts (HDFs) are still not completely understood. We undertook this study to investigate whether microRNA-155 (miR-155) directly regulates the expression of c-Jun in HDFs in vitro. METHODS: Expression of c-Jun mRNA and protein and miR-155 in UVA-irradiated HDFs were detected using quantitative real-time RT-PCR and Western blotting. Luciferase reporter assays were performed to examine whether a miR-155 binding site in the 3'-untranslated region (3'-UTR) of the c-Jun gene is responsible for miR-155-mediated c-Jun regulation in HEK293A cells, and expression of c-Jun mRNA and protein in UVA non-exposed and exposed HDFs trasfected with a miR-155 mimic or a miR-155 inhibitor was detected by quantitative real-time RT-PCR and Western blotting. RESULTS: Expression of miR-155 was markedly reduced and that of c-Jun mRNA and protein was significantly up-regulated in UVA-irradiated HDFs. Luciferase reporter assays indicated that c-Jun is a direct target of miR-155 in HEK293A cells. In both UVA non-exposed and exposed HDFs, miR-155 mimic decreased c-Jun protein levels, while miR-155 inhibitor increased c-Jun protein levels, but both had no effect on c-Jun mRNA expression, which suggest that miR-155-induced c-Jun inhibition occurs at the post-transcriptional level. CONCLUSIONS: Our results demonstrate that miR-155 directly controls c-Jun expression in HDFs at the post-transcriptional level and might function as a protective miRNA in HDFs.

Two novel frameshift mutations of the DSRAD gene in Chinese pedigrees with dyschromatosis symmetrica hereditaria.

BACKGROUND: Dyschromatosis symmetrica hereditaria (DSH) is an autosomal dominant disorder characterized by a mixture of hyperpigmented and hypopigmented macules localized on the back of the extremities and caused by the mutations in the DSRAD gene. METHODS: Two Chinese pedigrees of typical DSH were subjected to mutation detection in DSRAD. Direct sequencing of all PCR products of the whole coding regions of DSRAD was performed to identify the mutation. RESULTS: The c.1615delG (p.V539fs) mutation was found in the affected members but not in the healthy individuals in family 1 and the c.ins1372-9 CCACAGAT (p.D458fs) mutation was found in patients but not in the healthy members of family 2. CONCLUSION: Our study found two novel frameshift mutations in the DSRAD gene. We add new variants to the knowledge of DSRAD mutations in DSH.

Isolation and antitumor activities of acidic polysaccharide from Gynostemma pentaphyllum Makino.

Two acidic polysaccharides (GP-B1 and GP-C1) were obtained from Gynostemma pentaphyllum. The molecular weights (Mw) of the two fractions were 79 kDa for GP-B1 and 126 kDa for GP-C1. GP-B1 was composed of Gal, Ara, Man, Rha, Xyl, Glc, GalA and GlcA in a molar ration of 3.5:3.2:0.6:0.9:0.3:0.5:0.6:0.4. GP-C1 consisted of Gal, Ara, Man, Rha, Glc, and GlcA in the proportions of 2.1:1.0:0.3:0.5:0.4:0.9. Among them, GP-B1 treatment had a significant inhibitory effect on the growth of melanoma B16 in vivo and in vitro. Meanwhile GP-B1 could increase the relative spleen weight and stimulate the splenocyte proliferation alone or combined with ConA. Moreover, GP-B1 treatment induced an evident increase in the level of serum TNF-α, IFN-γ, and IL-12 and a reduction for IL-10 production. These results indicate that the antitumor effects of GP-B1 are associated with immunostimulation.

Purification of a polysaccharide from Gynostemma pentaphyllum Makino and its therapeutic advantages for psoriasis.

In current study, a water-soluble polysaccharide (GP-I), with a molecular mass of 33 kDa, was purified from Gynostemma pentaphyllum. Gas chromatography (GC) analysis suggested that it was composed of Glc, Gal, Man, Rha and Ara with a ratio of 5.3: 4.2: 3.0: 0.7: 0.8. The GP-I (25, 50, 100, 200 and 400 µg/ml) was found to have significant anti-proliferative effects on HaCat cells in a dose-dependent manner, as measured by MTT assay. On the contrary, Trypan blue exclusion experiment indicated that GP-I had no cytotoxicity to HaCat cells. Moreover, the decrease of mitochondrial membrane potential (MMP) in GP-I treated cells was also observed, indicating apoptosis in HaCat cells. Besides, tumor necrosis factor-α (TNF-α), a vital pro-inflammatory cytokine in psoriasis, in the supernatant of HaCat cells was dramatically reduced by GP-I. Collectively, these findings suggested that GP-I was a promising agent to be developed for psoriasis treatment in clinical therapy.

[Effect of curcumin on IL-17-induced nitric oxide production and expression of iNOS in human keratinocytes].

AIM: To investigate the effect of curcumin on IL-17-induced NO production, mRNA and protein expression of iNOS in human keratinocyte cell lines(HaCaT cells). METHODS: HaCaT cells were stimulated with IL-17 and incubated with three doses of curcumin for 24h in vitro. After collections of supernatant, total RNA and protein, NO levels in supernatant were detected and fluorescence quantitative PCR and Western blot were performed to determine the effect of curcumin on NO levels and iNOS. RESULTS: IL-17 increased NO levels, and expression of iNOS in HaCaT cells(P<0.01). Curcumin decreased IL-17 induced NO production and the iNOS expression at mRNA (P<0.01) and protein (P<0.01) levels significantly. CONCLUSION: Curcumin down-regulates IL-17-induced NO secretions and iNOS expression in HaCaT cells, thus provides a theoretical basis for the treatment of inflammatory diseases of skin related to keratinocytes.

Restoration of fragile histidine triad (FHIT) expression inhibits cell growth and induces apoptosis in cutaneous T-cell lymphoma cell line.

To investigate the effects of fragile histidine triad (FHIT) restoration on cell proliferation and apoptosis in human cutaneous T-cell lymphoma cell line, Hut-78, in vitro and in nude mouse. Wild-type FHIT gene was transfected by liposome into the Hut-78 cells. The alteration of cell growth curve and soft agar colony formation was studied in vitro and in nude mice. The FHIT gene was stably expressed in Hut-78 cells after the transfection. Compared with the controls, restoration of FHIT expression inhibited cell growth and induced apoptosis. Tumor formation in vivo was strongly suppressed by FHIT gene restoration. Our data demonstrate restoration of FHIT gene expression inhibit the tumor cell growth and provide an option for the treatment.

[Expression of CD1a and CD207 in condyloma acuminatum epidermis].

AIM: To investigate the expression of CD1a and CD207 in condyloma acuminatum (CA) epidermis and to understand its significance. METHODS: The mRNA expression of CD1a and CD207 in six CA epidermal lesions and in six normal controls were detected using oligonucleotide microarrys and confirmed by semi-quantitative RT-PCR, and the protein level of CD1a and CD207 in six CA epidermal lesions and in six normal controls were measured by Western blot. RESULTS: With microarrys, the mRNA expression of CD1a and CD207 were detected markedly down-regulated in six CA epidermal lesions as compared with that in six normal controls. Moreover, the down-regulation of CD1a and CD207 was verified by semi-quantitative RT-PCR. Western blot analysis showed that the protein expression of CD1a and CD207 in six CA epidermal lesions were significantly lower than that in normal controls. CONCLUSION: The expression of CD1a and CD207 is markedly down-regulated in CA epidermis compared with that in normal epidermis, and the results may suggest that the number of LC in CA epidermis is decreased and the function is impaired.

Apoptosis induced by synthetic retinoic acid CD437 on human melanoma A375 cells involves RIG-I pathway.

Human malignant melanoma is notoriously resistant to currently available pharmacological modulation. Our aim was to evaluate the anti-tumor effect of a novel synthetic retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carbo-xylic acid (CD437) on melanoma cell line A375. Analysis of cell morphology showed that CD437 promoted marked apoptosis in A375 cells. To explore the mechanisms of CD437-induced apoptosis, an NF-kappaB-luciferase reporter assay was performed, demonstrating that apoptosis induction by CD437 required activation of transcription factor NF-kappaB. Importantly, based on the findings that RIG-I (retinoic acid inducible gene I) can be induced by retinotic acid and can activate NF-kappaB through a CARD-containing adaptor protein VISA, we proposed a hypothesis that RIG-I was involved in the signal pathway of NF-kappaB activation induced by CD437 through the adaptor protein VISA. By specially cleaving VISA with hepatitis C virus (HCV) non-structural (NS)3/4A, the RIG-I pathway was blocked, with subsequent simultaneous inhibition of CD437-induced NF-kappaB activation and cell apoptosis in A375 cells. These results support our hypothesis and suggest that RIG-I may be a useful intermediate biologic marker for retinoid chemoprevention and treatment studies.

Effects of narrow-band ultraviolet B and tazarotene therapy on keratinocyte proliferation and TIG3 expression.

Tazarotene plus narrow-band ultraviolet B (NB-UVB) therapy has been shown to enhance the efficacy in treating patients with psoriasis, while the mechanism is not clear. The present study aims to investigate the alteration of cell proliferation and TIG3 in cultured normal human keratinocytes after NB-UVB and/or tazarotene treatment. Keratinocytes were exposed to NB-UVB, then incubated with or without tazarotene, and then cell proliferation was detected by methyl thiazoleterazolium colorimetric assay and TIG3 mRNA expression and protein production was examined by real-time reverse transcription polymerase chain reaction and immunocytochemistry, respectively. The results show that keratinocyte proliferation was inhibited and TIG3 mRNA expression and protein production were elevated by tazarotene at a dose higher than 0.1 micromol/L. In NB-UVB single irradiating groups, only 200 mJ/cm2 NB-UVB inhibited keratinocyte proliferation, and none of the irradiated groups had an effect on TIG3 expression. Moreover, tazarotene plus NB-UVB have stronger effects than those separately. These results indicate NB-UVB plus tazarotene may have synergistic effects on inhibiting keratinocyte proliferation and elevating TIG3 expression, which may have some implications for the understanding of how to treat psoriasis patients with tazarotene plus NB-UVB.

Downregulation of tazarotene induced gene-2 (TIG2) in skin squamous cell carcinoma.

Tazarotene, an RARbeta/gamma-selective synthetic retinoid, was found to induce three genes, tazarotene-induced genes (TIG) 1, 2 and 3. TIG2 was abundantly expressed in non-lesional psoriatic skin, but at lower levels in psoriatic lesions. The protein precursor encoded by TIG2, called prochemerin, can be converted into bioactive chemerin. Chemerin can then bind to chemerin receptor, resulting in chemoattracting dendritic cells and macrophages, and serving as a bridge between innate and adaptive immunity. Our objective was to investigate the role of TIG2 in skin squamous cell carcinoma (SCC). The levels of TIG2-protein and transcript in normal skin tissues, uninvolved skin and SCC lesions were determined by immunohistochemistry and in situ hybridization. TIG2-protein and transcript were detected in all layers of normal epidermis and uninvolved skin adjacent to SCC lesions. In addition, TIG2 was also expressed in the corneum, granular layers and the upper and middle layers of stratum spinosum of the marginal part of SCC lesions. On the other hand, TIG2-protein and transcript were barely detectable around the keratin pearls of SCC 1-2, and were not detectable at all in SCC 3-4.

[Alteration of tazarotene induced gene-2 expression in psoriasis vulgaris].

OBJECTIVE: To investigate the role of tazarotene induced gene-2 (TIG2) in psoriasis vulgaris. METHODS: TIG2 protein and mRNA expressions in normal tissues, psoriatic lesions and uninvolved skin tissues were detected by immunohistochemistry and in situ hybridization, respectively. RESULTS: TIG2 protein and mRNA were expressed in all the layers of normal and uninvolved epidermis. TIG2 expression was detected in the upper layers of the stratum spinosum of the marginal region of the psoriatic lesions, but not in the central area of the lesions. TIG2 expression was significantly lower in the basal layers of the central area of the paoriasis than that in the normal skin and uninvolved tissues (P < 0.01), and also lower in the marginal regions of the lesions (P < 0.01).The suprabasal layers of the marginal region in the lesion showed significantly lower TIG2 expression than the central area of the lesion (P < 0.01). CONCLUSION: TIG2 may maintain the normal differentiation of epidermal keratinocytes and implicate in the pathogenesis and development of psoriasis vulgaris.

[Alteration of retinoid X receptor alpha mRNA level after acitretin and/or narrow-band UVB treatment in normal human keratinocytes].

OBJECTIVE: To investigate the alteration of retinoid X receptor alpha (RXRalpha) mRNA level in normal human keratinocytes after acitretin and/or NB-UVB irradiation treatment. METHODS: After a 12-hour incubation with 10(-7)-10(-6) mol/L acitretin and/or following 50-100 mJ/cm2 NB-UVB irradiation in normal human keratinocytes, RXRalpha mRNA expression was examined by reverse transcription polymerase chain reaction (RT-PCR) and real-time quantitative RT-PCR. RESULTS: The expression of RXRalpha mRNA was obviously decreased by NB-UVB irradiation, but not by acitretion single treatment. When combining acitretin treatment with NB-UVB irradiation, greater decreased RXRalpha mRNA expression was observed than that of single treatment. CONCLUSION: Narrow-band UVB irradiation treatment can decrease RXRalpha mRNA expression, but not acitretin single treatment. Combining treatment with both can produce synergistic inhibition effects.

[Expression of E-cadherin, beta-catenin and cyclin D1 in epidermal skin lesions of patients with active psoriasis vulgaris].

OBJECTIVE: To examine the expressions of E-cadherin, beta-catenin and cyclin D1 in the skin lesions of patients with psoriasis vulgaris, and understand their possible roles in keratinocyte hyperproliferation in these patients. METHODS: Immunohistochemistry was performed to detect the expressions of E-cadherin, beta-catenin and cyclin D1 in the normal skin tissues and psoriatic lesions. RESULTS: In normal skin tissues, positive staining for E-cadherin and beta-catenin was detected in all layers of the normal epidermis at the sites of cell-cell junctions, and downregulation of E-cadherin and beta-catenin expression was found in the granular layer and basal layer of the psoriatic lesions. Cyclin D1 overexpression was observed mainly in the basal layer of the lesions, which was correlated to abnormal expression of beta-catenin. CONCLUSION: Downregulation of E-cadherin and beta-catenin expression and cyclin D1 overexpression in psoriatic skin are probably involved in keratinocyte hyperproliferation in psoriasis vulgaris.

[A novel retinoid CD437 induces apoptosis of human epidermoid carcinoma A431 cells].

OBJECTIVE: To investigate the effect of a novel retinoid CD437 and all-trans retinoic acid (ATRA) in inducing cell apoptosis and inhibiting the proliferation of human epidermoid carcinoma A431 cells and normal human epidermal keratinocytes. METHODS: MTT assay was used to determine the inhibitory effects of CD437 and ATRA on the growth of A431 cells and normal human epidermal keratinocytes, and the cell morphological changes were observed microscopically. Flow cytometry was used to investigate the effect of CD437 and ATRA on the cell cycle and apoptosis. RESULTS: CD437 was more effective than ATRA in inhibiting the proliferation of A431 cells and normal human epidermal keratinocytes. CD437 increased the percentage of sub-G1 populations in A431 cells and induced G1 arrest in normal human epidermal keratinocytes. ATRA appeared to be relatively ineffective for inducing apoptosis in A431 cells as compared to CD437. CD437 did not duce obvious apoptosis in normal human epidermal keratinocytes. CONCLUSION: CD437 is more effective than ATRA in inhibiting the proliferation and inducing apoptosis in A431 cells and shows selective apoptosis-inducing effect against malignant keratinocytes, suggesting its potential in the prevention or treatment of cutaneous carcinoma.

[Mutation detection of ATP2C1 gene in Chinese patients with Hailey-Hailey disease].

OBJECTIVE: To investigate the mutations of ATP2C1 gene in Chinese patients with Hailey-Hailey disease (HHD). METHODS: Genomic DNA was extracted from peripheral blood leukocytes. PCR and direct DNA sequencing were used to detect the mutations in all 27 exons of ATP2C1 gene in patients of two Chinese families and a sporadic patient with HHD. RESULTS: Three mutations in ATP2C1 gene were found, including 1 nonsense mutation, 1 deletion/frameshift mutation and 1 missense mutation. All of them were novel mutations. CONCLUSION: All the three mutations could affect the transcription and translation, and further the function of protein encoded by ATP2C1 gene.