2,336 research outputs found
Privacy-Aware Architectures for NFC and RFID Sensors in Healthcare Applications
World population and life expectancy have increased steadily in recent years, raising issues regarding access to medical treatments and related expenses. Through last-generation medical sensors, NFC (Near Field Communication) and radio frequency identification (RFID) technologies can enable healthcare internet of things (H-IoT) systems to improve the quality of care while reducing costs. Moreover, the adoption of point-of-care (PoC) testing, performed whenever care is needed to return prompt feedback to the patient, can generate great synergy with NFC/RFID H-IoT systems. However, medical data are extremely sensitive and require careful management and storage to protect patients from malicious actors, so secure system architectures must be conceived for real scenarios. Existing studies do not analyze the security of raw data from the radiofrequency link to cloud-based sharing. Therefore, two novel cloud-based system architectures for data collected from NFC/RFID medical sensors are proposed in this paper. Privacy during data collection is ensured using a set of classical countermeasures selected based on the scientific literature. Then, data can be shared with the medical team using one of two architectures: in the first one, the medical system manages all data accesses, whereas in the second one, the patient defines the access policies. Comprehensive analysis of the H-IoT system can be useful for fostering research on the security of wearable wireless sensors. Moreover, the proposed architectures can be implemented for deploying and testing NFC/RFID-based healthcare applications, such as, for instance, domestic PoCs
SARS-CoV-2 pandemic: An overview
By the end of May 2020, SARS-CoV-2 pandemic caused more than 350,000 deaths worldwide. In the first months, there have been uncertainties on almost any area: infection transmission route, virus origin and persistence in the environment, diagnostic tests, therapeutic approach, high-risk subjects, lethality, and containment policies. We provide an updated summary of the current knowledge on the pandemic, discussing the available evidence on the effectiveness of the adopted mitigation strategies
Advances in the set-up of a fluorescence- anisotropy assay for the search of novel inhibitors of the tead-4 complexes
Soil presence reduces the control effectiveness of a slow-release formulation of pyriproxyfen on Aedes aegypti (Diptera: Culicidae) larvae
Objective: To assess the influence of soil on the effectiveness of two new slow-release formulations (floating and non-floating) of pyriproxyfen coextruded with low-density polyethylene. Methods: Two slow-release devices were developed using low-density polyethylene, pyriproxyfen as larvicide and calcium carbonate as filler. A factorial design was used to evaluate the effect of soil presence on the performance of each device. Weekly bioassays were performed. Results: Soil presence affected treatment effectiveness, but this effect was associated with device type. The tablets were effective for nearly 3 months. Conclusion: Treatment effectiveness could be reduced because of the loss of pyriproxyfen by several physico-chemical processes such as adsorption into the soil.Fil: Junges, Melania Teresita. Consejo Nacional de Investigaciones CientÃficas y Técnicas; Argentina. Universidad Nacional de San MartÃn. Instituto de Investigaciones e IngenierÃa Ambiental. Laboratorio de EcologÃa de Enfermedades Transmitidas por Vectores; ArgentinaFil: Harburguer, Laura Vanesa. Consejo Nacional de Investigaciones CientÃficas y Técnicas. Unidad de Investigación y Desarrollo Estratégico para la Defensa. Ministerio de Defensa. Unidad de Investigación y Desarrollo Estratégico para la Defensa; ArgentinaFil: Lorenzo, Maria Cecilia. Instituto Nacional de TecnologÃa Industrial; Argentina. Universidad Nacional de San MartÃn. Instituto de Investigación e IngenierÃa Ambiental. - Consejo Nacional de Investigaciones CientÃficas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación e IngenierÃa Ambiental; ArgentinaFil: Eisenberg, Patricia. Universidad Nacional de San MartÃn. Instituto de Investigación e IngenierÃa Ambiental. - Consejo Nacional de Investigaciones CientÃficas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación e IngenierÃa Ambiental; Argentina. Instituto Nacional de TecnologÃa Industrial; ArgentinaFil: Masuh, Hector Mario. Consejo Nacional de Investigaciones CientÃficas y Técnicas. Unidad de Investigación y Desarrollo Estratégico para la Defensa. Ministerio de Defensa. Unidad de Investigación y Desarrollo Estratégico para la Defensa; ArgentinaFil: Carbajo, Anibal Eduardo. Universidad Nacional de San MartÃn. Instituto de Investigaciones e IngenierÃa Ambiental. Laboratorio de EcologÃa de Enfermedades Transmitidas por Vectores; Argentina. Consejo Nacional de Investigaciones CientÃficas y Técnicas; Argentin
Nutrient Analysis Critical Control Point (NACCP): Hazelnut as a Prototype of Nutrigenomic Study
A toolbox of biophysical and analytical assays helps to confirm the activity of novel hTS dimer disrupters (Ddis) with anticancer properties
Microbiota in the Natural History of Pancreatic Cancer: From Predisposition to Therapy
Simple Summary Pancreatic cancer is still burdened with a severe prognosis, despite advances in the diagnosis and surgical management of this disease. The gut microbiome is gaining increasing interest in the development and management in this setting. The intent of our review is to provide a comprehensive review for researchers and clinicians in the field to fully understand the role of the gut microbiome in the history of pancreatic cancer. We analyzed current literature from pre-cancerous conditions to cancer characteristics and how this may alter the therapeutic approach. Evidence and concerns can guide future research in this area. Early microbiome insights came from gut microbes and their role among intestinal and extraintestinal disease. The latest evidence suggests that the microbiota is a true organ, capable of several interactions throughout the digestive system, attracting specific interest in the biliopancreatic district. Despite advances in diagnostics over the last few decades and improvements in the management of this disease, pancreatic cancer is still a common cause of cancer death. Microbiota can influence the development of precancerous disease predisposing to pancreatic cancer (PC). At the same time, neoplastic tissue shows specific characteristics in terms of diversity and phenotype, determining the short- and long-term prognosis. Considering the above information, a role for microbiota has also been hypothesized in the different phases of the PC approach, providing future revolutionary therapeutic insights. Microbiota-modulating therapies could open new issues in the therapeutic landscape. The aim of this narrative review is to assess the most updated evidence on microbiome in all the steps regarding pancreatic adenocarcinoma, from early development to response to antineoplastic therapy and long-term prognosis
UHPLC-MS/MS screening of the hTEAD surface for the identification of novel allosteric inhibitors with anticancer activity
Antitarget, Anti-SARS-CoV-2 Leads, Drugs, and the Drug Discovery-Genetics Alliance Perspective
: The most advanced antiviral molecules addressing major SARS-CoV-2 targets (Main protease, Spike protein, and RNA polymerase), compared with proteins of other human pathogenic coronaviruses, may have a short-lasting clinical efficacy. Accumulating knowledge on the mechanisms underlying the target structural basis, its mutational progression, and the related biological significance to virus replication allows envisaging the development of better-targeted therapies in the context of COVID-19 epidemic and future coronavirus outbreaks. The identification of evolutionary patterns based solely on sequence information analysis for those targets can provide meaningful insights into the molecular basis of host-pathogen interactions and adaptation, leading to drug resistance phenomena. Herein, we will explore how the study of observed and predicted mutations may offer valuable suggestions for the application of the so-called "synthetic lethal" strategy to SARS-CoV-2 Main protease and Spike protein. The synergy between genetics evidence and drug discovery may prioritize the development of novel long-lasting antiviral agents
Designing selective Cys-ligands to unpair the binding of the Human Transcription Enhancer Associated Domain 4 (hTEAD-4) with its modulators to halt cancer cell growth
The Hippo Signalling cascade is an emerging target in tumour suppression regulation, neoplastic hypertrophy, and regenerative medicine. The pathway is activated by circulating anti-proliferative signals which leads to the phosphorylation of Yes Associated Protein (hYAP1) on Ser127/381, thus 14-3-3\u3c3 mediated cytosolic retention. Genetic alterations or exogenous factor may cause YAP nuclear migration and association to TEAD1-4 (Transcription Enhancer Associated Domain), triggering up-regulation of anti-apoptotic genes [1]. hTEAD is an enhancer that activates the nuclear transcription of genes as EMT\u2019s, EGFR and cyclins, and promotes the synthesis of survivin, tyrosine kinase HER3, and mitochondrial Bcl-xL involved in cell proliferation. TEAD binds a palmitic (palm) or myristic (myr) acids, tethered at Cys367 pocket, however its biological role is still not well known. hTEAD isoform-4 is the most represented of its family in solid tumours and its overexpression or mutation leads to cancer development and metastasis. Recent studies have considered hTEAD a promising target for anticancer drugs. Its inhibition strategy includes the disruption/prevention of YAP1:TEAD4 complex formation [2]. With the aim to develop a specific cysteine-directed inhibition strategy, we studied Cys on the protein surface and investigated their reactivity. Hence, our studies focus on characterizing the recombinant hTEAD4-ybd (aa217-434) surface though the analysis of the reactivity of its four Cys thiols (Cys310, Cys335, Cys367, Cys410), all close to YAP binding area. First, myr-Cys-367 was investigated to confirm the auto-myristoilation of the E. coli recombinant hTEAD4 through RP-chromatography on UHPLC-Orbitrap Q-Ex (ThermoFisher\u2122) by multicharged TIC deconvolution, and the total myr-TEAD was assessed around 25%. Myristate position was confirmed by FASP protein tryptic hydrolysis and tandem-MS peptide analysis. We studied hTEAD binding of a small disulphides and thiols library with different chemical properties through the exposed cysteines residues in presence of different concentration of reducing agent [3]. Top8 DDA (HCD)-MS/MS scan on the tryptic peptides suggested the ligands\u2019 high selectivity towards Cys335. Cys367 was never found conjugated, even in the non-Myr fraction, hinting the low accessibility to the lipid pocket. The number of surface reactive Cys was confirmed by a reverse-titration of the protein against increasing amount of thiophenol; excess of unreacted thiophenol was measured by HPLC-UV-ELSD (Agilent\u2122 1260), suggesting a 1:1 stoichiometry. We confirmed hTEAD-ybd ligand ratio by fluoresceine labelling with absorption and fluorescence differential spectroscopy. The ongoing work engages the screening of a larger compound library to study YAP:TEAD interaction with a ligand displacement assay of labelled TEAD to a rhodamine-tagged peptidomimetic probe to achieve structural information of the heterodimer interface and to start a hit-optimization programme.
REFERENCES
[1] Santucci M, Vignudelli T, et al. The Hippo Pathway and YAP/TAZ-TEAD Protein-Protein Interaction as Targets for Regenerative Medicine and Cancer Treatment. J Med Chem. 2015 Jun 25;58(12):4857-73.
[2] Elisi G.M, Santucci M, et al. Repurposing of Drugs Targeting YAP-TEAD Functions. Cancers 2018, 10, 329.
[3] Malpezzi G MSc Degree Thesis, Solvent exposure, and reactivity of the cysteines of Transcription Enhancer Associate Domain (TEAD), a potential anticancer target, 2021. University of Pavia \u2013 University of Modena and Reggio Emilia
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