Background: Hypoxia is a characteristic of solid tumors that can lead to tumor angiogenesis and early metastasis, and addressing hypoxia presents tremendous challenges. In this work, a nanomedicine based on oxygen-absorbing perfluorotributylamine (PFA) and the bioreductive prodrug tirapazamine (TPZ) was prepared by using a polydopamine (PDA)-coated UiO-66 metal organic framework (MOF) as the drug carrier. Results: The results showed that TPZ/PFA@UiO-66@PDA nanoparticles significantly enhanced hypoxia, induced cell apoptosis in vitro through the oxygen-dependent HIF-1α pathway and decreased oxygen levels in vivo after intratumoral injection. In addition, our study demonstrated that TPZ/PFA@UiO-66@PDA nanoparticles can accumulate in the tumor region after tail vein injection and effectively inhibit tumor growth when combined with photothermal therapy (PTT). TPZ/PFA@UiO-66@PDA nanoparticles increased HIF-1α expression while did not promote the expression of CD31 in vivo during the experiment. Conclusions: By using TPZ and PFA and the enhanced permeability and retention effect of nanoparticles, TPZ/PFA@UiO-66@PDA can target tumor tissues, enhance hypoxia in the tumor microenvironment, and activate TPZ. Combined with PTT, the growth of osteosarcoma xenografts can be effectively inhibited. Graphic

Psoriasis is a multifactorial, inflammatory, skin disease associated with various comorbidities. The cost of those comorbidities is not well characterized. The present study assesses the incremental burden of comorbidities on healthcare resource utilization, direct costs and indirect costs associated with short-term disabilities among patients with psoriasis in the United States. A retrospective, U.S. cohort analysis was conducted using a large claims database. Adult psoriasis patients with at least two diagnoses of psoriasis during the years 2010 and 2011 (one psoriasis diagnosis had to happen in the year 2010) and with continuous enrollment of medical and pharmacy benefits in the years 2010 and 2011 were included. Psoriasis patients were categorized and compared according to the presence or absence of pre-selected comorbidities in the year 2010. Adjusted annual direct (costs associated with outpatient, emergency room, and inpatient claims, and outpatient pharmacy claims) and indirect costs (short-term disabilities) was assessed in patients with and without comorbidities using a regression analysis, controlling for age, gender, and psoriasis severity in year 2010. In total, 56,406 patients (mean [SD]) age, 51.6 [14.6] years) were included in the analysis. The most prevalent comorbidities were hypertension (34.3%), hyperlipidemia (33.5%), cardiovascular disease (17.7%), diabetes (14.2%), and psoriatic arthritis (9.9%). Psoriasis patients with comorbidities used more healthcare resources than those without comorbidities. The incidence rate ratio (IRR) (95% CI) for patients with cardiovascular disease was 1.5 (1.4 − 1.5) for outpatient visits, 2.6 (2.4 − 2.8) for hospitalizations, and 2.3 (2.2 − 2.5) for ER visits, showing higher IRRs across all three types of resource use. The mean annual adjusted direct cost differences (i.e., incremental adjusted costs) in psoriasis patients with and without comorbidities were $9914.3, $8386.5, and $8275.1 for psoriatic arthritis, peripheral vascular disease, and cardiovascular disease, respectively. The mean annual incremental adjusted indirect costs of short-term disabilities were $1333, $1195, $994.9, and $996.6 for cerebrovascular disease, obesity, peripheral vascular disease, and depression, respectively. The presence of comorbidities was associated with higher healthcare resource utilization and costs among patients with psoriasis.

Background/Aim: Secreted phosphoprotein 24 kD (spp24) has been shown to inhibit bone morphogenetic protein 2 (BMP2)-induced cancer growth in several tumor models. In this study, we aimed to investigate the effects spp24 on the growth of prostate cancer caused by BMP2 in vitro and in vivo. Materials and Methods: The effects of BMP2 and spp24 on PC-3 cell viability were analyzed using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay. A subcutaneous tumor model and intratibial tumor model was established using PC-3 cells. Tumor growth was assessed through gross examination and radiography during the experiment. Then, after sacrifice, tumor cell apoptosis and tumor cell proliferation were assessed by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay and immunochemical analysis. Results: BMP2 stimulated the PC-3 cell proliferation in vitro and spp24 could abolish the effect of BMP2. In a xeneograft tumor model, BMP2 promoted the subcutaneous and intratibial tumor growth, while spp24 dramatically inhibited the tumor growth induced by BMP2. Histological examination showed that spp24 also abolished the BMP2-induced proliferating cell nuclear antigen (PCNA) expression and promoted tumor cell apoptosis. Conclusion: Spp24 can inhibit the growth of prostate cancer and its bone metastasis induced by BMP2; spp24 may have great potential to be a therapeutic agent in clinical situations.

Multiple sclerosis (MS) is a chronic disease that affects mainly adults in the prime of their lives. However, few studies report the impact of high annual relapse rates on outcomes. The purpose of this study was to identify high relapse activity (HRA) in patients with MS, comparing differences in outcomes between patients with and without HRA.