IMPORTANCE Children with psoriasis are at increased risk for comorbidities. Many children with psoriasis are also overweight or obese; it is unknown whether the increased risk of comorbidities in these children is independent of obesity. OBJECTIVE To determine the risk of elevated lipid levels (hyperlipidemia/hypertriglyceridemia), hypertension, metabolic syndrome, polycystic ovarian syndrome, diabetes, nonalcoholic liver disease, and elevated liver enzyme levels in children with and without psoriasis, after accounting for obesity. DESIGN, SETTING, AND PARTICIPANTSThis was a retrospective cohort study of claims data from Optum Laboratories Data Warehouse (includes 150 million privately insured and Medicare enrollees). A cohort of 29 957 children with psoriasis (affected children) and an age-, sex-, and race-matched comparator cohort of 29 957 children without psoriasis were identified and divided into 4 groups: (1) nonobese, without psoriasis (reference cohort);(2) nonobese, with psoriasis; (3) obese, without psoriasis; and (4) obese, with psoriasis. MAIN OUTCOMES AND MEASURES Risk of developing comorbidities (Cox proportional hazards regression). RESULTSThe overall mean (SD) age of those included in the cohort was 12.0 (4.4) years, and 16 034 (53.5%) were girls. At baseline, more affected children were obese (862 [2.9%] vs 463 [1.5%]; P < .001 for all comparisons). Children with psoriasis were significantly more likely to develop each of the comorbidities than those without psoriasis (P < .01). Obesity was a strong risk factor for development of each comorbidity, even in those without psoriasis (hazard ratios [HRs] ranging from 2.26 to 18.11). The risk of comorbidities was 40% to 75% higher among nonobese children with vs without psoriasis: elevated lipid levels (HR, 1.42; 95% CI, 1.25-1.62), hypertension (HR, 1.64; 95% CI, 1.40-1.93), diabetes (HR, 1.58; 95% CI, 1.27-1.95), metabolic syndrome (HR, 1.62; 95% CI, 1.13-2.33), polycystic ovarian syndrome (HR, 1.49; 95% CI, 1.18-1.88), nonalcoholic liver disease (HR, 1.76; 95% CI, 1.16-2.65), and elevated liver enzyme levels (HR, 1.46; 95% CI, 1.27-1.67). Except for hypertension (P = .03), no significant interaction occurred between psoriasis and obesity on the risk of comorbidities.CONCLUSIONS AND RELEVANCE Children with psoriasis are at greater risk of developing obesity, hyperlipidemia, hypertension, diabetes, metabolic syndrome, polycystic ovarian syndrome, nonalcoholic liver disease, and elevated liver function enzyme levels than children without psoriasis. While psoriasis is a small independent risk factor for the development of these comorbidities, obesity is a much stronger contributor to comorbidity development in children with psoriasis.

Breast cancer remains a serious threaten to the women’s health, discovery of potent treatment would help to improve the outcomes of breast cancer patients. Harmine extracted from Peganum harmala L, has been reported to exert tumor suppressive activity in several malignancies. Our objective was to demonstrate the effects of harmine on the malignant phenotypes of breast cancer cells. Breast cancer cell lines (MDA-MB-231, SKBR3, and MCF-7) and human normal breast cell line MCF-10A were employed in the present study. The MTT and colony formation assays were applied to the detection of cell viability and proliferation. Wound healing and transwell assays were performed to evaluate the alterations of cell migration and invasion after harmine treatment. Flow cytometry was applied to assess the effect of harmine in inducing cell apoptosis. Furthermore, western blotting assay was used to detect the biomarkers of epithelial-mesenchymal transition and phosphatidylinositol 3 kinase (PI3K) signaling pathway. The tumorigenesis ability was detected by subcutaneous implantation. Harmine dose-dependently suppressed the viability and proliferative capacity of breast cancer cells. Flow cytometry showed that harmine induced apoptosis in MCF-7 and MDA-MB-231 cells. In addition, harmine effectively inhibited the migration and invasion abilities of breast cancer cells. Western blotting indicated harmine significantly promoted E-cadherin and PTEN expression, while suppressed N-cadherin, vimentin, PI3K, p-mTOR, and AKT levels. Interfering the PTEN expression by siRNA partly rescued the activity of PI3K signaling pathway. Moreover, harmine injection also suppressed the tumorigenesis of breast cancer cells. Our results suggested that Hermine could suppress multiple malignant phenotypes and inhibit PI3K signaling, which supports that harmine might be a potential tumor-suppressive natural compound against breast cancer.

Background We aimed to establish an osteosarcoma prognosis prediction model based on a signature of endoplasmic reticulum stress-related genes. Methods Differentially expressed genes (DEGs) between osteosarcoma with and without metastasis from The Cancer Genome Atlas (TCGA) database were mapped to ERS genes retrieved from Gene Set Enrichment Analysis to select endoplasmic reticulum stress-related DEGs. Subsequently, we constructed a risk score model based on survival-related endoplasmic reticulum stress DEGs and a nomogram of independent survival prognostic factors. Based on the median risk score, we stratified the samples into high- and low-risk groups. The ability of the model was assessed by Kaplan–Meier, receiver operating characteristic curve, and functional analyses. Additionally, the expression of the identified prognostic endoplasmic reticulum stress-related DEGs was verified using real-time quantitative PCR (RT-qPCR). Results In total, 41 endoplasmic reticulum stress-related DEGs were identified in patients with osteosarcoma with metastasis. A risk score model consisting of six prognostic endoplasmic reticulum stress-related DEGs (ATP2A3, ERMP1, FBXO6, ITPR1, NFE2L2, and USP13) was established, and the Kaplan–Meier and receiver operating characteristic curves validated their performance in the training and validation datasets. Age, tumor metastasis, and the risk score model were demonstrated to be independent prognostic clinical factors for osteosarcoma and were used to establish a nomogram survival model. The nomogram model showed similar performance of one, three, and five year-survival rate to the actual survival rates. Nine immune cell types in the high-risk group were found to be significantly different from those in the low-risk group. These survival-related genes were significantly enriched in nine Kyoto Encyclopedia of Genes and Genomes pathways, including cell adhesion molecule cascades, and chemokine signaling pathways. Further, RT-qPCR results demonstrated that the consistency rate of bioinformatics analysis was approximately 83.33%, suggesting the relatively high reliability of the bioinformatics analysis. Conclusion We established an osteosarcoma prediction model based on six prognostic endoplasmic reticulum stress-related DEGs that could be helpful in directing personalized treatment.