In a published case-control study (GSE152075) from SARS-CoV-2 positive (n=403) and negative patients (n=50), we analyzed the response to infection assessing gene expression of host cell receptors and antiviral proteins. The expression analysis associated with reported risk factors for COVID-19 was also assessed. SARS-CoV-2 cases had higher ACE2 , but lower TMPRSS2, BSG/CD147 and CTSB expression compared with negative cases. COVID-19 patients’ age negatively affected ACE2 expression. MX1 and MX2 were higher in COVID-19 patients. A negative trend for MX1 and MX2 was observed as patients’ age increased. Principal Component Analysis determined that ACE2 , MX1 , MX2, and BSG/CD147 expression was able to cluster non-COVID-19 and COVID-19 individuals. Multivariable regression showed that MX1 expression significantly increased for each unit of viral load increment. Altogether, these findings support differences in ACE2 , MX1 , MX2, and BSG/CD147 expression between COVID-19 and non-COVID-19 patients and point out to MX1 as a critical responder in SARS-CoV-2 infection.

The adult zebrafish is considered a useful model for studying mechanisms involved in tissue growth and regeneration. We have characterized cytotoxic damage to the retina of adult zebrafish caused by the injection of cobalt chloride (CoCl ) into the vitreous cavity. The CoCl concentration we used primarily caused injury to photoreceptors. We observed the complete disappearance of cones, followed by rods, across the retina surface from 28 to 96 hr after CoCl injury. The loss of 30% of bipolar cells was also observed by 50 hr after lesion (hpl). CoCl injury provoked a strong induction of the proliferative activity of multipotent Müller glia and derived progenitors. The effect of CoCl on retina cells was significantly reduced by treatment with glutamate ionotropic receptor antagonists. Cone photoreceptor regeneration occurred 25 days after injury. Moreover, a single dose of CoCl induced vascular damage and regeneration, whereas three injections of CoCl administered weekly provoked neovascular-like changes 20 days after injury. CoCl injury also caused microglial reactivity in the optic disc, retina periphery and fibre layer. CoCl -induced damage enhanced pluripotency and proneural transcription factor gene expression in the mature retina 72 hpl. Tumour necrosis factor alpha, vascular endothelial growth factor (VEGF) and VEGF receptor mRNA levels were also significantly enhanced by 72 hpl. The injury paradigm we have described in this work may be useful for the discovery of signalling molecules and pathways that participate in the regenerative response and it may serve as a model to screen for compounds that could potentially treat aberrant angiogenesis.

Background: Prostate cancer (PCa) dissemination shows a tendency to develop in the bone, where heme oxygenase 1 (HO-1) plays a critical role in bone remodeling. Previously by LC/ESI-MSMS, we screened for HO-1 interacting proteins and identified annexin 2 (ANXA2). The aim of this study was to analyze the relevance of ANXA2/HO-1 in PCa and bone metastasis. Methods: We assessed ANXA2 levels using a co-culture transwell system of PC3 cells (pre-treated or not with hemin, an HO-1 specific inducer) and the pre-osteoclastic Raw264.7 cell line. Results: Under co-culture conditions, ANXA2 mRNA levels were significantly modulated in both cell lines. Immunofluorescence analysis unveiled a clear ANXA2 reduction in cell membrane immunostaining for Raw264.7 under the same conditions. This effect was supported by the detection of a decrease in Ca 2+ concentration in the conditioned medium. HO-1 induction in tumor cells prevented both, the ANXA2 intracellular relocation and the decrease in Ca 2+ concentration. Further, secretome analysis revealed urokinase (uPA) as a key player in the communication between osteoclast progenitors and PC3 cells. To assess the clinical significance of ANXA2/HO-1, we performed a bioinformatics analysis and identified that low expression of each gene strongly associated with poor prognosis in PCa regardless of the clinico-pathological parameters assessed. Further, these genes appear to behave in a dependent manner. Conclusions: ANXA2/HO-1 rises as a critical axis in PCa.Biomolecules 2020, 10, 467 2 of 24 microenvironment communicate and interact with each other to develop a fertile niche for the promotion of the metastatic process [3][4][5].Evidence has recognized inflammation as a risk factor for this neoplastic disease [6]. Heme oxygenase 1 (HO-1), encoded by the HMOX1 gene, is a stress response protein and a critical mediator of cellular homeostasis [7]. Although the role of HO-1 in cancer is controversial [8,9], we have shown that its pharmacologic or genetic upregulation is associated with a less aggressive phenotype in PCa [10]. HO-1 impairs tumor growth and angiogenesis in vivo and downregulates the expression of target genes associated with inflammation in PCa [11,12]. In the metastatic bone site, we demonstrated that HO-1 is capable of modulating signaling pathways relevant to skeletal PCa metastasis, such as FoxO/β-catenin and promotes bone remodeling when human tumor cells are transplanted into the femur of SCID mice [13]. Moreover, we have shown the direct effect of HO-1 on bone turnover and remodeling. When assessing the physiological impact of Hmox1 gene knockout on bone metabolism in vivo, histomorphometric analysis of Hmox1−/− mice bones exhibited significantly decreased bone density. A positive correlation between Hmox1 expression and key bone markers was observed in primary mouse osteoblasts (PMOs) [14]. These observations highlight the importance of HO-1 expression in bone, not only for the physiology of bone cells but also in the modulation of the communication between PMOs and PC...