The amyloid precursor protein (APP) is a transmembrane glycoprotein central to Alzheimer’s disease (AD) with functions in brain development and plasticity, including in neurogenesis and neurite outgrowth. Epidermal growth factor (EGF) and heparin-binding EGF-like growth factor (HB-EGF) are well-described neurotrophic and neuromodulator EGFR ligands, both implicated in neurological disorders, including AD. Pro-HB-EGF arose as a putative novel APP interactor in a human brain cDNA library yeast two-hybrid screen. Based on their structural and functional similarities, we first aimed to verify if APP could bind to (HB-)EGF proforms. Here, we show that APP interacts with these two EGFR ligands, and further characterized the effects of APP-EGF interaction in ERK activation and neuritogenesis. Yeast co-transformation and co-immunoprecipitation assays confirmed APP interaction with HB-EGF. Co-immunoprecipitation also revealed that APP binds to cellular pro-EGF. #link# Overexpression of HB-EGF in HeLa cells, or exposure of SH-SY5Y cells to EGF, both resulted in increased APP protein levels. EGF and APP were observed to synergistically activate the ERK pathway, crucial for neuronal differentiation. Immunofluorescence analysis of cellular neuritogenesis in APP overexpression and EGF exposure conditions confirmed a synergistic effect in promoting the number and the mean length of neurite-like processes. Synergistic ERK activation and neuritogenic effects were completely blocked by the EGFR inhibitor PD 168393, implying APP/EGF-induced activation of EGFR as part of the mechanism. This work shows novel APP protein interactors and provides a major insight into the APP/EGF-driven mechanisms underlying neurite outgrowth and neuronal differentiation, with potential relevance for AD and for adult neuroregeneration.

Extramural vascular invasion (EMVI) is a poor prognostic factor in colon cancer. However, the benefit of adjuvant chemotherapy in patients with EMVI is not well defined. The objective of this study is to determine if there is a survival benefit for using adjuvant chemotherapy in patients with EMVI-positive colon cancers.

We performed a retrospective review of all patients with stages II and III colon adenocarcinoma who underwent surgical resection between 2004 and 2015. Cox regression was used to determine the effect of chemotherapy on EMVI-positive patients while adjusting for the extent of invasion, regional lymph node metastasis, histologic grade, age, site of tumor, and ASA score.

A total of 750 patients were included in this study. Extramural vascular invasion was present in 93 out of 387 stage II patients (24%) and 187 out of 363 stage III patients (52%). The Cox regression model showed that in patients with EMVI, those who did not receive adjuvant chemotherapy had a 1.6-fold (1.1-2.3) increase in the hazard of death compared with those who received chemotherapy.

click here who were EMVI-negative fared better than those who were EMVI-positive. In patients who were EMVI-positive, adjuvant chemotherapy improved overall survival.

Patients who were EMVI-negative fared better than those who were EMVI-positive. In patients who were EMVI-positive, adjuvant chemotherapy improved overall survival.Determining the minimum image resolution needed for clinical assessment is crucial for computational efficiency, image standardization, and storage needs alleviation. In this paper, we explore the image resolution requirements for the assessment of alopecia by analyzing how clinicians detect the presence of characteristics needed to quantify the disorder in the clinic. By setting the image resolution as a function of width of the patient’s head, we mimicked experiments conducted in the computer vision field to understand human perception in the context of scene recognition and object detection and asked 6 clinicians to identify the regions of interest on a set of retrospectively collected de-identified images at different resolutions. The experts were able to detect the presence of alopecia at very low resolutions, while significantly higher resolution was required to identify the presence of vellus-like hair. Furthermore, the accuracy with which alopecia was detected as a function of resolution followed the same trend as the one obtained when we classified normal versus abnormal hair density using a standard neural network architecture, hinting that the resolution needed by an expert human observer may also provide an upper bound for future image processing algorithms.Acute kidney injury (AKI) is the most common complication of sepsis with a high mortality rate. In this study, we focus on the renal injury caused by the immune response of renal tubular epithelial cells and inflammation-induced renal tubular epithelial cell apoptosis. We studied the role of GRP120 in the inflammation and apoptosis of human renal cell line HK-2 and mouse primary renal tubular epithelial cells. GPR120 agonist GW9508 activated the GPR120 pathway. Inflammatory factors were detected using quantitative real-time PCR and enzyme-linked immunosorbent assay. Cell apoptosis experiments included the annexin V and PI double-staining method combined with flow cytometry, TUNEL method, and Western blot. The level of cytokines including TNF-α, IL-6, IL-1β, and iNOS was significantly decreased (P  less then  0.05) in HK-2 and TECs after the activation of the GPR120 pathway. Besides, the cell apoptosis of both cells increased. Overexpressed GPR120 and shGPR120 were established. Treatment with lipopolysaccharide (LPS) increased the level of cytokines including TNF-α, IL-6, IL-1β, and iNOS in HK-2 cell and TECs. Compared with control-LPS and negative control (NC)-LPS, the overexpression of GPR120 and shGPR120 could decrease and increase the level of secreted cytokines significantly (P less then  0.05), respectively, after LPS-induced apoptosis. After H2O2- and LPS-induced apoptosis, respectively, compared with the control and NC groups, overexpressed GPR120 and shGPR120 could reduce and increase the expression of caspase-3, respectively. GPR120 could suppress the cellular immune response and apoptosis in renal tubular epithelial cells, thereby possibly protecting the kidney and relieving sepsis-induced AKI.