Action of HMGB1 on miR221/222 cluster in neuroblastoma cell lines

microRNA (miR/miRNA) are small non-coding RNAs that control gene expression at the post-transcriptional level by targeting mRNAs. Aberrant expression of miRNAs is often observed in different types of cancer. Specific miRNAs function as tumor suppressors or oncogenes and interfere with various aspects of carcinogenesis, including differentiation, proliferation and invasion. Upregulation of miRNAs 221 and 222 has been shown to induce a malignant phenotype in numerous human cancers via inhibition of phosphatase and tensin homolog (PTEN) expression. Neuroblastoma is the most common extracranial solid malignancy in children, which is characterized by cellular heterogeneity that corresponds to different clinical outcomes. The different cellular phenotypes are associated with different gene mutations and miRs that control genetic and epigenetic factors. For this reason miRs are considered a potential therapeutic target in neuroblastoma. The aim of the present study was to investigate the mechanisms by which extracellular high mobility group box 1 (HMGB1) promotes cell growth in neuroblastoma. SK-N-BE(2) and SH-SY5Y neuroblastoma derived cell lines were transfected with the antisense oligonucleotides, anti-miR-221 and -222, followed by treatment with HMGB1 to investigate the expression of the oncosuppressor PTEN. In this study, it was demonstrated that HMGB1, which is released by damaged cells and tumor cells, upregulates miR-221/222 oncogenic clusters in the two human neuroblastoma derived cell lines. The results revealed that the oncogenic cluster miRs 221/222 were more highly expressed by the most undifferentiated cell line [SK-N-BE(2)] compared with the the less tumorigenic cell line (SH-SY5Y) and that exogenous HMGB1 increases this expression. In addition, HMGB1 modulates PTEN expression via miR-221/222, as demonstrated by transiently blocking miR-221/222 with anti-sense oligonucleotides. These results may lead to the development of novel therapeutic strategies for neuroblastoma

ARCHAEOLOGICAL MATERIALS FROM GABII (CENTRAL ITALY): KNOWLEDGE OF OFFERINGS AND RITUALS AT THE INFANT BURIALS THROUGH AN INTEGRATED APPROACH

The ancient Latin city of Gabii is situated 18 km (11.2 miles) to the east of Rome (Central Italy) along the modern Via Prenestina. Gabii was a renowned city in Roman times, particularly during the Republican period and there are various influences in the site that can be identified in Roman culture itself. Gabii is also one of the most significant and important archaeological sites in the territory of the Municipality of Rome and due to its characteristics, it represents today an extraordinary research context. From the excavations carried out in the past it is possible to see how, under the soil, the main structures and buildings of the ancient city are still largely preserved. Among the various testimonies of the past, the tombs, and the micro and macro remains that these contain, represent an opportunity to investigate such practices in the context of Early Iron Age and Orientalizing Latium. In particular, the finds from the Area D baby burials of Gabii enriched the existing dataset so far significantly, allowing us to explore funerary ritual behavior in a more systematic way. This work reports the results of the detailed examination of four tombs (Tombs 30, 50, 51 and 52) of archaeological site. The field strategy for the excavation of the tombs was geared from the start towards both the systematic retrieval of archaeobotanical and zooarchaeological remains and the sampling for organic residue analysis. Aiming for total recovery, the sediments from the tomb fills were sifted in their entirety as their stratigraphic excavation progressed, and samples were taken for flotation. This careful screening allowed for the detection of concentrations of organic material that represent plant and/or animal depositions. The excavation and removal of the grave goods was carried out following strict protocols for residue sampling, minimizing the risk of organic contamination. Samples were analysed by High Temperature Gas Chromatography/Mass Spectrometry (HTGC/MS) and Gas chromatography/Combustion/Isotope ratio mass spectrometry (GC-C-IRMS). For each burial, a subset of vessels including both closed and open shapes was selected, such as cups, open bowl without foot, amphoretta, amphora with dots, Kantharos, plate on a foot, olla, and olpe in bucchero. The results demonstrate the still largely unexploited potential of this sort of integrated studies, encouraging us to expand the application of chemical methods to contexts from other well–controlled excavations

Characterization of Super-Responder Profile in Chronic Plaque Psoriatic Patients under Guselkumab Treatment: A Long-Term Real-Life Experience

background: the term "super responder" identifies a group of patients who exhibit a rapid and optimal response to biological treatment compared to the overall treated population. the primary objective of our study is to characterize this subgroup of patients to enable the early identification of those who will respond most effectively to the proposed treatment while also evaluating clinical efficacy. methods: this retrospective study evaluated 232 patients treated with guselkumab in monotherapy for at least 20 weeks between november 2018 and november 2023. patients were divided into two groups: those who achieved complete clear skin (PASI = 0) during the first 20 weeks of treatment were defined as super responders (SRe) and non-super responders (nSRe) were the remaining patients. PASI was assessed at weeks 0, 4, and subsequently every eight weeks. predictors of the SRe status were evaluated by univariate and multivariate logistic regression analyses. results: the univariate analyses showed that patients with psoriatic arthritis at the baseline, bio-na & iuml;ve patients, or those who had not received an interleukin (IL) 17 inhibitor as their last therapy before guselkumab administration were more likely to be super responders to the proposed treatment. multivariate logistic analysis models suggested that the combination of psoriatic arthritis at the baseline and the bio-na & iuml;ve condition was the strongest predictive model for the SRe status. at week 204, the main difference between the two groups concerned the achievement of PASI100, maintained by 86.8 of SRe compared to 62.8% of nSRe. conclusions: the efficacy and safety of guselkumab are confirmed in our real-life experience. Identifying the SRe status will undoubtedly play a role in clinical practice and the therapeutic decision-making algorithm

Glucose-6-phosphate dehydrogenase plays a crucial role in the protection from redox-stress induced apoptosis.

Glucose-6-phosphate dehydrogenase-deleted embryonic stem (ES) cells (G6pdD) proliferate in vitro without special requirements, but when challenged with oxidants fail to sustain glutathione disulphide reconversion to reduced glutathione (GSH), entering a condition of oxidative stress. Here, we investigate the signalling events downstream of GSH oxidation in G6pdD and wild-type (wt) ES cells. We found that G6pdD ES cells are very sensitive to oxidants, activating an apoptotic pathway at oxidant concentrations otherwise sublethal for wt ES cells. We show that the apoptotic pathway activated by low oxidant concentrations is accompanied by mitochondria dysfunction, and it is therefore blocked by the overexpression of Bcl-XL. Bcl-XL does not inhibit the decrease in cellular GSH and reactive oxygen species formation following oxidant treatment. We also found that oxidant treatment in ES cells is followed by the activation of the MEK/ extracellular signal-regulated kinase (ERK) pathway. Interest¬ingly, ERK activation has opposite outcomes in G6pdD ES cells compared to wt, which has a proapoptotic function in the first and a prosurvival function in the latter. We show that this phenomenon can be regulated by the cellular GSH level

Scaling up health knowledge at European level requires sharing integrated data: An approach for collection of database specification

Computerized health care databases have been widely described as an excellent opportunity for research. The availability of “big data” has brought about a wave of innovation in projects when conducting health services research. Most of the available secondary data sources are restricted to the geographical scope of a given country and present heterogeneous structure and content. Under the umbrella of the European Innovation Partnership on Active and Healthy Ageing, collaborative work conducted by the partners of the group on “adherence to prescription and medical plans” identified the use of observational and large-population databases to monitor medication-taking behavior in the elderly. This article describes the methodology used to gather the information from available databases among the Adherence Action Group partners with the aim of improving data sharing on a European level. A total of six databases belonging to three different European countries (Spain, Republic of Ireland, and Italy) were included in the analysis. Preliminary results suggest that there are some similarities. However, these results should be applied in different contexts and European countries, supporting the idea that large European studies should be designed in order to get the most of already available databases

1053pdgenomics features gf and integration with mri radiomics features rf to develop a prognostic model in oral cavity squamous cell carcinoma oscc

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A dashboard-based system for supporting diabetes care

[EN] Objective To describe the development, as part of the European Union MOSAIC (Models and Simulation Techniques for Discovering Diabetes Influence Factors) project, of a dashboard-based system for the management of type 2 diabetes and assess its impact on clinical practice. Methods The MOSAIC dashboard system is based on predictive modeling, longitudinal data analytics, and the reuse and integration of data from hospitals and public health repositories. Data are merged into an i2b2 data warehouse, which feeds a set of advanced temporal analytic models, including temporal abstractions, care-flow mining, drug exposure pattern detection, and risk-prediction models for type 2 diabetes complications. The dashboard has 2 components, designed for (1) clinical decision support during follow-up consultations and (2) outcome assessment on populations of interest. To assess the impact of the clinical decision support component, a pre-post study was conducted considering visit duration, number of screening examinations, and lifestyle interventions. A pilot sample of 700 Italian patients was investigated. Judgments on the outcome assessment component were obtained via focus groups with clinicians and health care managers. Results The use of the decision support component in clinical activities produced a reduction in visit duration (P¿¿¿.01) and an increase in the number of screening exams for complications (P¿<¿.01). We also observed a relevant, although nonstatistically significant, increase in the proportion of patients receiving lifestyle interventions (from 69% to 77%). Regarding the outcome assessment component, focus groups highlighted the system¿s capability of identifying and understanding the characteristics of patient subgroups treated at the center. Conclusion Our study demonstrates that decision support tools based on the integration of multiple-source data and visual and predictive analytics do improve the management of a chronic disease such as type 2 diabetes by enacting a successful implementation of the learning health care system cycle.This work was supported by the European Union in the Seventh Framework Programme, grant number 600914.Dagliati, A.; Sacchi, L.; Tibollo, V.; Cogni, G.; Teliti, M.; Martinez-Millana, A.; Traver Salcedo, V.... (2018). A dashboard-based system for supporting diabetes care. Journal of the American Medical Informatics Association. 25(5):538-547. https://doi.org/10.1093/jamia/ocx159S538547255Sim, I., Gorman, P., Greenes, R. A., Haynes, R. B., Kaplan, B., Lehmann, H., & Tang, P. C. (2001). Clinical Decision Support Systems for the Practice of Evidence-based Medicine. Journal of the American Medical Informatics Association, 8(6), 527-534. doi:10.1136/jamia.2001.0080527Palmer, A. 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A bio-guided assessment of the anti-inflammatory activity of hop extracts (Humulus lupulus L. cv. Cascade) in human gastric epithelial cells

The present work aims to characterize and investigate the anti-inflammatory activity of hop extracts (cv. Cascade) in an in vitro model of gastric inflammation. The biological activities of hydroalcoholic and aqueous extracts from cones were evaluated by comparing IL-8 inhibition induced by TNF\u3b1. The hydroalcoholic extract demonstrated a higher inhibitory effect, which was just slightly affected by an in vitro simulated gastric digestion. The identification of active compounds was performed by a bio-guided fractionation which afforded 11 fractions, one of which inhibited IL-8 release in a concentration-dependent fashion in human gastric epithelial AGS cells. Phytochemical analysis revealed xanthohumol A and xanthohumol D as the main active components. The present study provides some experimental evidences that Humulus lupulus L. may exert an anti-inflammatory activity on the gastric district by the inhibition of the IL-8 secretion, partially due to its prenylated chalcones content