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Burns and chronic wounds are especially challenging wounds to heal. In efforts to heal these wounds, physicians often use autologous skin grafts to help restore mechanical and barrier functionality to the wound area. These grafts are, by nature, limited in availability. In an effort to provide an alternative, we have developed an electrospun wound dressing designed to incorporate into the wound with the option to deliver a cellular payload. Here, a blend of poly(glycolic acid) and poly(ethylene glycol) was electrospun as part of a custom fabrication method that incorporated 3D printed poly(vinyl alcohol) sacrificial elements. This preparation is unique compared to traditional electrospinning as sacrificial elements provide an internal void space for an injectable payload to be delivered to the wound site. When the construct was tested in vivo (full thickness excisional skin wounds), wound closure was slightly delayed by the presence of the scaffold in both normal and challenged wounds. Quality of healing was improved in normal wounds as measured by histomorphometrics when treated with the construct and exhibited increased neovascularization. learn more Our results demonstrate that the extracellular matrix-like scaffold developed in this study is beneficial to healing of full thickness skin defects and may benefit challenged wounds. © 2020 Wiley Periodicals, Inc.Triple negative breast cancer (TNBC) possesses highly aggressive phenotype, treatment with limited options, and a poor prognosis. In this study, we examined the therapeutic effect of anti-claudin (CLDN)-4 extracellular domain antibody, 4D3, on TNBC. When the expression of CLDN4 and CLDN1 in invasive ductal carcinoma (IDC) was examined in 114 IDCs (78 cases from 2004 to 2009 in a single center and 36 cases of tissues array), CLDN1 had lower expression than CLDN4 and correlated with histological grade. In contrast, expression of CLDN4 correlated with histological grade, receptor subtype, and stage. CLDN4 expression in human IDC cell lines MCF-7 (luminal subtype) and MDA-468 (TNBC) was at the same level. In both cells, paclitaxel (PTX)-induced growth suppression was enhanced by 4D3. Furthermore, 4D3 increased both intracellular PTX concentration (in both cells) and apoptosis. In the mouse model, 4D3 promoted the antitumor effect of PTX on subcutaneous tumors and reduced lung metastasis. The combination of PTX and 4D3 reduced M2 macrophages and mesenchymal stem cells in the tumor. 4D3 also reduced stemness of the tumors in association with increase in the intratumoral pH. Moreover, concurrent treatment of 4D3, PTX, or tamoxifen; or with PTX and tamoxifen in MDA-468 also showed the same level of antitumor activity and survival as MCF-7. Furthermore, in bone metastasis model, combination of PTX and bisphosphonate with 4D3 promoted tumor growth in both cells. Thus, CLDN4 targeting of the antibody facilitated existing therapeutic effects. This article is protected by copyright. All rights reserved.BACKGROUND & AIMS Nonalcoholic fatty liver disease (NAFLD) and chronic hepatitis B (CHB) are common liver diseases. Concurrent NAFLD may affect antiviral treatment outcomes in CHB patients. The aim of this study is to investigate the impact of NAFLD on complete viral suppression ([CVS], HBV DNA .05), but NAFLD had higher cumulative rates of CVS + BR, compared with non-NAFLD patients (32.5% vs 22.8%, P = .03). In multivariate analyses, NAFLD was not independently associated with CVS and/or BR outcomes. Receipt of entecavir or tenofovir (vs older therapies) and lower baseline HBV DNA or higher ALT were positively associated with achieving CVS or BR. CONCLUSION Concomitant NAFLD had no impact on the long-term rates of CVS and/or BR in treated CHB patients. © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.OBJECTIVE To analyse populational trends and perioperative complications following conservative surgery versus oophorectomy in women less then 50 years of age with ovarian torsion. DESIGN Population-based retrospective observational study. SETTING Nationwide Inpatient Sample in the USA (2001-2015). POPULATION In all, 89 177 ovarian torsions including 20 597 (23.1%) conservative surgeries and 68 580 (76.9%) oophorectomies. METHODS (1) Trend analysis to assess utilisation of conservative surgery over time, (2) multivariable binary logistic regression to identify independent factors associated with conservative surgery, and (3) inverse probability of treatment weighting with a generalised estimating equation to analyze perioperative complications. MAIN OUTCOME MEASURES Trends, characteristics, and complications related to conservative surgery. RESULTS Performance of conservative surgery increased from 18.9 to 25.1% between 2001 and 2015 (32.8% relative increase, P = 0.001) but decreased steadily after age 15, agists.Tumor angiogenesis is an important therapeutic target in colorectal cancer (CRC). We aimed to identify novel genes associated with angiogenesis in CRC. Using RNA-sequencing analysis in normal and tumor endothelial cells (TECs) isolated from primary CRC tissues, we detected frequent upregulation of adipocyte enhancer-binding protein 1 (AEBP1) in TECs. Immunohistochemical analysis revealed that AEBP1 is upregulated TECs and stromal cells in CRC tissues. Quantitative RT-PCR analysis showed that there is little or no AEBP1 expression in CRC cell lines, but that AEBP1 is well expressed in vascular endothelial cells. Levels of AEBP1 expression in human umbilical vein endothelial cells (HUVECs) were upregulated by tumor conditioned medium derived from CRC cells or by direct co-culture with CRC cells. AEBP1 knockdown suppressed proliferation, migration and in vitro tube formation by HUVECs. In xenograft experiments, AEBP1 knockdown suppressed tumorigenesis and microvessel formation. Depletion of AEBP1 in HUVECs downregulated a series of genes associated with angiogenesis or endothelial function, including aquaporin 1 (AQP1) and periostin (POSTN), suggesting that AEBP1 may promote angiogenesis through regulation of those genes. These results suggest that upregulation of AEBP1 contributes to tumor angiogenesis in CRC, which makes AEBP1 a potentially useful therapeutic target. This article is protected by copyright. All rights reserved.
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