Skeletal development requires the correct balance of osteoblast proliferation, survival, and differentiation which is modulated by a network of signaling pathways and transcription factors. We have examined the role of the AKT (PKB), and ERK1/2 signaling pathways in the osteoblast response to FGFs, which inhibit differentiation, and to IGF-1 and Wnt signaling, which promote it. Using osteoblastic cell lines as well as primary calvarial osteoblasts, we show that ERK1/2 and AKT have distinct effects in FGF-induced osteoblast proliferation and differentiation. ERK1/2 is a primary mediator of FGF-induced proliferation, but also contributes to osteoblast differentiation, while AKT is important for osteoblast survival. Signaling by IGF-1, that promotes osteoblast differentiation, strongly activates AKT and weakly ERK1/2, while the opposite results are obtained with FGF, which inhibits differentiation. By introducing a constitutively active form of AKT, we found that increased AKT activity drives osteoblasts to differentiation. Increasing the AKT signal in osteoblasts that harbor FGFR2 activating mutations, found in Crouzon (342Y) and Apert (S22W) syndromes, is also able to drive differentiation in these cells, that normally fail to differentiate. Wnt signals, that promotes differentiation, also induce AKT phosphorylation, and cells expressing active AKT have increased levels of stabilized beta-catenin, a central molecule in Wnt signaling. Our results indicate that the relative strengths of ERK and AKT signaling pathways determine whether osteoblasts are driven into proliferation or differentiation, and that the effects of AKT may be due, in part, to synergy with the Wnt pathway as well as with the Runx2 transcription factor.
Globally, at the time of writing (20 March 2021), 121.759.109 confirmed COVID-19 cases have been reported to the WHO, including 2.690.731 deaths. Globally, on 18 March 2021, a total of 364.184.603 vaccine doses have been administered. In Italy, 3.306.711 confirmed COVID-19 cases with 103.855 deaths have been reported to WHO. In Italy, on 9 March 2021, a total of 6.634.450 vaccine doses have been administered. On 15 March 2021, Italian Medicines Agency (AIFA) decided to temporarily suspend the use of the AstraZeneca COVID-19 vaccine throughout the country as a precaution, pending the rulings of the European Medicines Agency (EMA). This decision was taken in line with similar measures adopted by other European countries due to the death of vaccinated people. On 18 March 2021, EMA’s safety committee concluded its preliminary review about thromboembolic events in people vaccinated with COVID-19 Vaccine AstraZeneca at its extraordinary meeting, confirming the benefits of the vaccine continue to outweigh the risk of side effects, however, the vaccine may be associated with very rare cases of blood clots associated with thrombocytopenia, i.e., low levels of blood platelets with or without bleeding, including rare cases of cerebral venous thrombosis (CVT). We report the case of a 54-year-old woman who developed disseminated intravascular coagulation (DIC) with multi-district thrombosis 12 days after the AstraZeneca COVID-19 vaccine administration. A brain computed tomography (CT) scan showed multiple subacute intra-axial hemorrhages in atypical locations, including the right frontal and the temporal lobes. A plain old balloon angioplasty (POBA) of the right coronary artery was performed, without stent implantation, with restoration of distal flow, but with persistence of extensive thrombosis of the vessel. A successive thorax angio-CT added the findings of multiple contrast filling defects with multi-vessel involvement: at the level of the left upper lobe segmental branches, of left interlobar artery, of the right middle lobe segmental branches and of the right interlobar artery. A brain magnetic resonance imaging (MRI) in the same day showed the presence of an acute basilar thrombosis associated with the superior sagittal sinus thrombosis. An abdomen angio-CT showed filling defects at the level of left portal branch and at the level of right suprahepatic vein. Bilaterally, it was adrenal hemorrhage and blood in the pelvis. An evaluation of coagulation factors did not show genetic alterations so as the nasopharyngeal swab ruled out a COVID-19 infection. The patient died after 5 days of hospitalization in intensive care.
The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has already assumed pandemic proportions, affecting over 100 countries in few weeks. A global response is needed to prepare health systems worldwide. Covid-19 can be diagnosed both on chest X-ray and on computed tomography (CT). Asymptomatic patients may also have lung lesions on imaging. CT investigation in patients with suspicion Covid-19 pneumonia involves the use of the high-resolution technique (HRCT). Artificial intelligence (AI) software has been employed to facilitate CT diagnosis. AI software must be useful categorizing the disease into different severities, integrating the structured report, prepared according to subjective considerations, with quantitative, objective assessments of the extent of the lesions. In this communication, we present an example of a good tool for the radiologist (Thoracic VCAR software, GE Healthcare, Italy) in Covid-19 diagnosis (Pan et al. in Radiology, 2020. https ://doi.org/10.1148/radio l.20202 00370 ). Thoracic VCAR offers quantitative measurements of the lung involvement. Thoracic VCAR can generate a clear, fast and concise report that communicates vital medical information to referring physicians. In the post-processing phase, software, thanks to the help of a colorimetric map, recognizes the ground glass and differentiates it from consolidation and quantifies them as a percentage with respect to the healthy parenchyma. AI software therefore allows to accurately calculate the volume of each of these areas. Therefore, keeping in mind that CT has high diagnostic sensitivity in identifying lesions, but not specific for Covid-19 and similar to other infectious viral diseases, it is mandatory to have an AI software that expresses objective evaluations of the percentage of ventilated lung parenchyma compared to the affected one.
This article provides an overview of imaging assessment of ablated pancreatic cancer. Only studies reporting radiological assessment on pancreatic ablated cancer were retained. We found 16 clinical studies that satisfied the inclusion criteria. Radiofrequency ablation and irreversible electroporation have become established treatment modalities because of their efficacy, low complication rates, and availability. Microwave Ablation (MWA) has several advantages over radiofrequency ablation (RFA), which may make it more attractive to treat pancreatic cancer. Electrochemotherapy (ECT) is a very interesting emerging technique, characterized by low complication rate and safety profile. According to the literature, the assessment of the effectiveness of ablative therapies is difficult by means of the Response Evaluation Criteria in Solid Tumors (RECIST) criteria that are not suitable to evaluate the treatment response considering that are related to technique used, the timing of reassessment, and the imaging procedure being used to evaluate the efficacy. RFA causes various appearances on imaging in the ablated zone, correlating to the different effects, such as interstitial edema, hemorrhage, carbonization, necrosis, and fibrosis. Irreversible electroporation (IRE) causes the creation of pores within the cell membrane causing cell death. Experimental studies showed that Diffusion Weigthed Imaging (DWI) extracted parameters could be used to detect therapy effects. No data about functional assessment post MWA is available in literature. Morphologic data extracted by Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) do not allow to differentiate partial, complete, or incomplete response after ECT conversely to functional parameters, obtained with Position Emission Tomography (PET), MRI, and CT.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.