Escaping the Network Longo, Anna
Open Philosophy,
05/2020, Letnik:
3, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Abstract
We are today agents of a peculiar reality, the global network or the system for automated information production. Our condition in the global network is that of agents of the real, since we ...all contribute to the coproduction of this ever-evolving process. Nevertheless, I will argue, this reality is but the effect of the adoption of a notion of instrumental pragmatic rationality which denies the existence of any other possible reality as the actualization of different determinations of Reason. While following Deleuze s notion of deterritorialization, I ll show that the real philosophical choice does not concern the introduction of new moves that create differentiations within a universal game, but that it is concerned with the possible abolition of the agency which is instantiated within the collective network.
A pericyte-like differentiation of human adipose-derived mesenchymal stem cells (ASCs) was tested in in vitro experiments for possible therapeutic applications in cases of diabetic retinopathy (DR) ...to replace irreversibly lost pericytes. For this purpose, pericyte-like ASCs were obtained after their growth in a specific pericyte medium. They were then cultured in high glucose conditions to mimic the altered microenvironment of a diabetic eye. Several parameters were monitored, especially those particularly affected by disease progression: cell proliferation, viability and migration ability; reactive oxygen species (ROS) production; inflammation-related cytokines and angiogenic factors. Overall, encouraging results were obtained. In fact, even after glucose addition, ASCs pre-cultured in the pericyte medium (pmASCs) showed high proliferation rate, viability and migration ability. A considerable increase in mRNA expression levels of the anti-inflammatory cytokines transforming growth factor-β1 (TGF-β1) and interleukin-10 (IL-10) was observed, associated with reduction in ROS production, and mRNA expression of pro-inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), and angiogenic factors. Finally, a pmASC-induced better organization of tube-like formation by retinal endothelial cells was observed in three-dimensional co-culture. The pericyte-like ASCs obtained in these experiments represent a valuable tool for the treatment of retinal damages occurring in diabetic patients.
Graphene oxide (GO) is a bidimensional novel material that exhibits high biocompatibility and angiogenic properties, mostly related to the intracellular formation of reactive oxygen species (ROS). In ...this work, we set up an experimental methodology for the fabrication of GO@peptide hybrids by the immobilization, via irreversible physical adsorption, of the Ac-(GHHPH)
-NH
peptide sequence, known to mimic the anti-angiogenic domain of the histidine-proline-rich glycoprotein (HPRG). The anti-proliferative capability of the graphene-peptide hybrids were tested in vitro by viability assays on prostate cancer cells (PC-3 line), human neuroblastoma (SH-SY5Y), and human retinal endothelial cells (primary HREC). The anti-angiogenic response of the two cellular models of angiogenesis, namely endothelial and prostate cancer cells, was scrutinized by prostaglandin E2 (PGE
) release and wound scratch assays, to correlate the activation of inflammatory response upon the cell treatments with the GO@peptide nanocomposites to the cell migration processes. Results showed that the GO@peptide nanoassemblies not only effectively induced toxicity in the prostate cancer cells, but also strongly blocked the cell migration and inhibited the prostaglandin-mediated inflammatory process both in PC-3 and in HRECs. Moreover, the cytotoxic mechanism and the internalization efficiency of the theranostic nanoplatforms, investigated by mitochondrial ROS production analyses and confocal microscopy imaging, unraveled a dose-dependent manifold mechanism of action performed by the hybrid nanoassemblies against the PC-3 cells, with the detection of the GO-characteristic cell wrapping and mitochondrial perturbation. The obtained results pointed out to the very promising potential of the synthetized graphene-based hybrids for cancer therapy.
Vascular pericytes are an important cellular component in the tumor microenvironment, however, their role in supporting cancer invasion is poorly understood. We hypothesized that PDGF-BB could be ...involved in the transition of human retinal pericytes (HRPC) in cancer-activated fibroblasts (CAF), induced by the 92.1 uveal melanoma (UM) cell line. In our model system, HRPC were conditioned by co-culturing with 92.1UM for 6 days (cHRPC), in the presence or absence of imatinib, to block PDGF receptor-β (PDGFRβ). The effects of the treatments were tested by wound healing assay, proliferation assay, RT-PCR, high-content screening, Western blot analysis, and invasion assay. Results showed profound changes in cHRPC shape, with increased proliferation and motility, reduction of NG2 and increase of TGF-β1, α-SMA, vimentin, and FSP-1 protein levels, modulation of PDGF isoform mRNA levels, phospho-PDGFRβ, and PDGFRβ, as well as phospho-STAT3 increases. A reduction of IL-1β and IFNγ and an increase in TNFα, IL10, and TGF-β1, CXCL11, CCL18, and VEGF mRNA in cHRPC were found. Imatinib was effective in preventing all the 92.1UM-induced changes. Moreover, cHRPC elicited a significant increase of 92.1UM cell invasion and active MMP9 protein levels. Our data suggest that retinal microvascular pericytes could promote 92.1UM growth through the acquisition of the CAF phenotype.
Stem cell-based treatments have been extensively explored in the last few decades to develop therapeutic strategies aimed at providing effective alternatives for those human pathologies in which ...surgical or pharmacological therapies produce limited effects. Among stem cells of different sources, mesenchymal stem cells (MSCs) offer several advantages, such as the absence of ethical concerns, easy harvesting, low immunogenicity and reduced tumorigenesis risks. Other than a multipotent differentiation ability, MSCs can release extracellular vesicles conveying proteins, mRNA and microRNA. Thanks to these properties, new therapeutic approaches have been designed for the treatment of various pathologies, including ocular diseases. In this review, the use of different MSCs and different administration strategies are described for the treatment of diabetic retinopathy, glaucoma, and retinitis pigmentosa. In a large number of investigations, positive results have been obtained by
in vitro
experiments and by MSC administration in animal models. Most authors agree that beneficial effects are likely related to MSC paracrine activity. Based on these considerations, many clinical trials have already been carried out. Overall, although some adverse effects have been described, promising outcomes are reported. It can be assumed that in the near future, safer and more effective protocols will be developed for more numerous clinical applications to improve the quality of life of patients affected by eye diseases.
Patients affected by myelofibrosis (MF) or polycythemia vera (PV) and treated with ruxolitinib are at high risk for severe coronavirus disease 2019. Now a vaccine against the virus SARS-CoV-2, which ...is responsible for this disease, is available. However, sensitivity to vaccines is usually lower in these patients. Moreover, fragile patients were not included in large trials investigating the efficacy of vaccines. Thus, little is known about the efficacy of this approach in this group of patients. In this prospective single-center study, we evaluated 43 patients (30 MF patients and 13 with PV) receiving ruxolitinib as a treatment for their myeloproliferative disease. We measured anti-spike and anti-nucleocapsid IgG against SARS-CoV2 15-30 days after the second and the third BNT162b2 mRNA vaccine booster dose. Patients receiving ruxolitinib showed an impaired antibody response to complete vaccination (2 doses), as 32.5% of patients did not develop any response. After the third booster dose with Comirnaty, results slightly improved, as 80% of these patients produced antibodies above the threshold positivity. However, the quantity of produced antibodies was well below that reached than those reported for healthy individuals. PV patients elicited a better response than patients affected by MF. Thus, different strategies should be considered for this high-risk group of patients.
Du point de vue de la logique cognitive, il n’est pas si facile qu’on le croit de récuser la rationalité des théories du complot. Les dénonciateurs du conspirationnisme partagent souvent une même ...conception simpliste de la vérité avec ceux auxquels ils croient s’opposer. Cet article suggère que c’est plutôt du côté d’une bifurcation écologique radicale qu’on pourra trouver une alternative réelle au tourniquet dans lequel sont pris ensemble conspirationnistes et anti-conspirationnistes.
Reactive oxygen species (ROS) accumulation plays a pivotal role in the onset of cell damage induced by hyperglycemia and represents one of the major factors in the pathogenesis of diabetic ...retinopathy. In this study, we tested the antioxidants cyanidin-3-O-glucoside (C3G) and verbascoside (Verb) in the protection of retinal endothelium against glucose toxicity "
".
Increasing amounts (5-50 μM) of C3G, Verb or the combination of both compounds were tested in Human Retinal Endothelial Cells (HREC) grown with normal glucose (5 mM, NG) or high glucose (25 mM, HG).
Reduced cell viability and enhanced ROS levels (evaluated by MTT and H2DCFDA assays, respectively) in HG-stimulated HREC were restored by C3G and Verb in a dose-dependent manner, achieving the maximum protection in the presence of both compounds. Moreover, co-treatment with C3G and Verb worked better than each single molecule alone in the prevention of the disruption of blood-retinal-barrier-like properties by HG in a confluent HREC monolayer, as assessed by trans endothelial electrical resistance (TEER) and Na-Fluorescein permeability assays. Accordingly, C3G and Verb together also better counteracted the HG-induced down-regulation of the tight junction membrane proteins Zonula Occludens-1 and VE-Cadherin evaluated by immunocytochemical and Western blot analyses.
In conclusion, our data indicate that C3G and Verb could efficiently protect the retinal endothelium against high glucose damage.
The wide use of ruxolitinib, approved for treating primary and secondary myelofibrosis (MF), has revolutionized the landscape of these diseases. This molecule can reduce spleen volume and ...constitutional symptoms, guaranteeing patients a better quality of life and survival or even a valid bridge to bone marrow transplantation. Despite a rapid response within the first 3 to 6 months of treatment, some patients fail to achieve a significant benefit or lose early response. After ruxolitinib failure, new drugs are available to provide an additional therapeutic option for these patients. However, the correct timing point for deciding on a therapy shift is still an open challenge. Recently, a clinical prognostic score named RR6 (Response to Ruxolitinib after 6 months) was proposed to determine survival after 6 months of treatment with ruxolitinib in patients affected by MF. We applied this model to a cohort of consecutive patients treated at our center to validate the results obtained in terms of median overall survival (mOS): for the low-risk class, mOS was not reached (as in the training cohort); for the intermediate-risk, mOS was 52 months (95% CI 39-106); for the high-risk, it was 33 (95% 8.5-59). Moreover, in addition to the other studies present in the literature, we evaluated how the new RR6 score could better identify primary MF patients at high risk, with a slight or no agreement compared to DIPSS, contrary to what occurs in secondary MF. Thus, we were able to confirm the predictive power of the RR6 model in our series, which might be of help in guiding future therapeutic choices.
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