Betulinic acid decreases ER-negative breast cancer cell growth in vitro and in vivo: role of Sp transcription factors and microRNA-27a:ZBTB10.

Betulinic acid (BA), a pentacyclic triterpenoid isolated from tree bark is cytotoxic to cancer cells. There is evidence that specificity proteins (Sps), such as Sp1, Sp3, and Sp4, are overexpressed in tumors and contribute to the proliferative and angiogenic phenotype associated with cancer cells. The objective of this study was to determine the efficacy of BA in decreasing the Sps expression and underlying mechanisms. Results show that BA decreased proliferation and induced apoptosis of estrogen-receptor-negative breast cancer MDA-MB-231 cells. The BA-induced Sp1, Sp3, and Sp4 downregulation was accompanied by increased zinc finger ZBTB10 expression, a putative Sp-repressor and decreased microRNA-27a levels, a microRNA involved in the regulation of ZBTB10. Similar results were observed in MDA-MB-231 cells transfected with ZBTB10 expression plasmid. BA induced cell cycle arrest in the G2/M phase and increased Myt-1 mRNA (a microRNA-27a target gene), which causes inhibition in G2/M by phosphorylation of cdc2. The effects of BA were reversed by transient transfection with a mimic of microRNA-27a. In nude mice with xenografted MDA-MB-231 cells, tumor size and weight were significantly decreased by BA treatment. In tumor tissue, ZBTB10 mRNA was increased while mRNA and protein of Sp1, Sp3 and Sp4, as well as mRNA of vascular endothelial growth factor receptor (VEGFR), survivin and microRNA-27a were decreased by BA. In lungs of xenografted mice, human ß2-microglobulin mRNA was decreased in BA-treated animals. These results show that the anticancer effects of BA are at least in part based on interactions with the microRNA-27a-ZBTB10-Sp-axis causing increased cell death.

Validation of CORE-MD PMS Support Tool: A Novel Strategy for Aggregating Information from Notices of Failures to Support Medical Devices' Post-Market Surveillance.

INTRODUCTION: The EU Medical Device Regulation 2017/745 defines new rules for the certification and post-market surveillance of medical devices (MD), including an additional review by Expert Panels of clinical evaluation data for high-risk MD if reports and alerts suggest possibly associated increased risks. Within the EU-funded CORE-MD project, our aim was to develop a tool to support such process in which web-accessible safety notices (SN) are automatically retrieved and aggregated based on their specific MD categories and the European Medical Device Nomenclature (EMDN) classification by applying an Entity Resolution (ER) approach to enrich data integrating different sources. The performance of such approach was tested through a pilot study on the Italian data. METHODS: Information relevant to 7622 SN from 2009 to 2021 was retrieved from the Italian Ministry of Health website by Web scraping. For incomplete EMDN data (68%), the MD best match was searched within a list of about 1.5 M MD on the Italian market, using Natural Language Processing techniques and pairwise ER. The performance of this approach was tested on the 2440 SN (32%) already provided with the EMDN code as reference standard. RESULTS: The implemented ER method was able to correctly assign the correct manufacturer to the MD in each SN in 99% of the cases. Moreover, the correct EMDN code at level 1 was assigned in 2382 SN (97.62%), at level 2 in 2366 SN (96.97%) and at level 3 in 2329 SN (95.45%). CONCLUSION: The proposed approach was able to cope with the incompleteness of the publicly available data in the SN. In this way, grouping of SN relevant to a specific MD category/group/type could be used as possible sentinel for increased rates in reported serious incidents in high-risk MD.

Quorum Quenching and Microbial Control through Phenolic Extract of Eugenia Uniflora Fruits.

We describe the characterization of the centesimal composition, mineral and phenolic content of Eugenia uniflora fruit and the determination of the antioxidant, antimicrobial and quorum quenching activities of the pulp phenolic extract. Centesimal composition was determined according to standard methods; trace elements were measured by total reflection X-ray fluorescence spectroscopy. The phenolic compounds were extracted by solid-phase chromatography and quantified by spectrophotometry. Antioxidant activity was determined by using 3 different methods. Antimicrobial activity was evaluated against a panel of foodborne microorganisms and antiquorum sensing activity in Chromobacterium violaceum was performed by measuring inhibition of quorum sensing dependent violacein production. The centesimal composition (per 100 g of pulp) was as follows: protein 3.68 ± 0.21 g, lipids 0.02 ± 0.03 g, carbohydrates 10.31 g and fiber 2.06 g. Trace elements (mg/g of pulp) were determined as: K 0.90, Ca 3.36, Fe 0.60, Zn 0.17, Cl 0.56, Cr 0.06, Ni 0.04, and Cu 0.07. The pulp is a source of phenolic compounds and presents antioxidant activity similar to other berries. The fruit phenolic extract inhibited all tested bacteria. We also found that the fruit phenolic extract at low subinhibitory concentrations inhibited up to 96% of violacein production in C. violaceum, likely due to the fruit's phenolic content. This study shows the contribution of E. uniflora phenolic compounds to the antioxidant, antimicrobial and the newly discovered quorum quenching activity, all of which could be used by the food and pharmaceutical industries to develop new functional products.

Modelling, designing, and implementing a family-based health record prototype.

Within the arising and fast growing trend of the personalized healthcare, the promising Personalized Health Informatics (PHI) asks to be understood, modelled, implemented, and tested. The central idea of "keeping healthy lifestyle", that grounds the development of PHI systems, needs to be extended to the digital family group, where the middle generation (the "parents") manages the responsibility of taking care and improving the health of the weaker members (children and grandparents). The family environment is also a fundamental indicator of disease risk. We modelled, designed, and implemented a prototype for the health data management in a multigenerational family environment.

Anticarcinogenic effects of polyphenolics from mango (Mangifera indica) varieties.

Many polyphenolics contained in mango have shown anticancer activity. The objective of this study was to compare the anticancer properties of polyphenolic extracts from several mango varieties (Francis, Kent, Ataulfo, Tommy Atkins, and Haden) in cancer cell lines, including Molt-4 leukemia, A-549 lung, MDA-MB-231 breast, LnCap prostate, and SW-480 colon cancer cells and the noncancer colon cell line CCD-18Co. Cell lines were incubated with Ataulfo and Haden extracts, selected on the basis of their superior antioxidant capacity compared to the other varieties, where SW-480 and MOLT-4 were statistically equally most sensitive to both cultivars followed by MDA-MB-231, A-549, and LnCap in order of decreasing efficacy as determined by cell counting. The efficacy of extracts from all mango varieties in the inhibition of cell growth was tested in SW-480 colon carcinoma cells, where Ataulfo and Haden demonstrated superior efficacy, followed by Kent, Francis, and Tommy Atkins. At 5 mg of GAE/L, Ataulfo inhibited the growth of colon SW-480 cancer cells by approximately 72% while the growth of noncancer colonic myofibroblast CCD-18Co cells was not inhibited. The growth inhibition exerted by Ataulfo and Haden polyphenolics in SW-480 was associated with an increased mRNA expression of pro-apoptotic biomarkers and cell cycle regulators, cell cycle arrest, and a decrease in the generation of reactive oxygen species. Overall, polyphenolics from several mango varieties exerted anticancer effects, where compounds from Haden and Ataulfo mango varieties possessed superior chemopreventive activity.

A Web-based system for family health record.

During the past few years, a new and fast growing trend, defined as Personalized healthcare (pHealth) rose. It concerns the individualization of prevention, treatment and well being procedures available through the healthcare system. pHealth is realized through a number of capabilities stemming from the micro and nanosciences, information and communication technologies (ICTs). Electronic health record is one of them. Electronic health records are a fundamental support needed not only by healthcare providers, but also for individual patients. The idea of individuals collecting, organizing, and keeping in file folders their own paper-based medical information is not new. The widespread diffusion of the ICTs and the Internet has made this idea feasible using personal computers, personal digital assistants or smart-phones. We considered the management of healthcare data in the familiar environment and we designed and developed a system for family health record. The system permits an easy compilation and provides an effective visualization of the clinical data concerning family members also for friendly printing tasks.

Impacto da luz, pH, ácido ascórbico e glicose na estabilidade de antocianinas da fonte não usual maria-pretinha (solanum americanum, mill) / Impact of light, pH, ascorbic acid and glucose on the stability of supply anthocyanins unsual mary shine (solanum americanum, mill)

O fruto de maria-pretinha (Solanum americanum) consiste em fonte não usual, porém viável de produção de antocianinas. Sendo assim, objetivou-se avaliar a estabilidade do extrato antociânico obtido dessa fonte vegetal, após extração com metanol acidificado (0,05% HCl), frente a fatores degradativos como luz, pH, ácido ascórbico e glicose. Sua estabilidade foi estimada determinando-se os valores de absorbância no comprimento de onda de máxima absorção em função do tempo, mediante os quais foram calculadas as constantes de velocidade de degradação (k) e o tempo de meia-vida (t1/2) de cada sistema. Os efeitos da luz e da concentração de 400 ppm de ácido ascórbico foram os mais destrutivos para a cor do pigmento, especialmente em pH 4,0. A adição de ácido ascórbico acelerou a degradação do pigmento antociânico. A glicose não afetou a estabilidade das antocianinas. Os pigmentos apresentaram maior estabilidade em pH 2,0. A interação negativa de ácido ascórbico e antocianinas merece mais investigações, já que a aplicação de pigmentos antociânicos na indústria de alimentos, especialmente em sucos e refrigerantes, mostrou-se bastante promissora.

Correlação entre métodos espectrofotométricos e colorimétricos na determinação da foto e termossensibilidade dos carotenoides de tomate / Correlation between spectrophotometric and colorimetric methods for determination of photosensitivity and thermosensitivity of tomato carotenoids

A busca por pigmentos naturais para aplicação em alimentos e o desafio de sua produção industrial tem motivado pesquisadores a investigar sua estabilidade à luz, temperatura, pH e oxigênio. Mistura de licopeno, obtida de polpa de tomate e óleo mineral, foi preparada para se estudar a foto e termossensibilidade do corante. Determinações espectrofotométricas e colorimétricas foram realizadas durante o período de estocagem. O efeito da luz foi mais destrutivo que a maior temperatura avaliada (80 graus C), sobretudo pela descoloração brusca de algumas amostras após 30 dias de estocagem. O pigmento foi pouco afetado quando armazenado no escuro e a 40 graus C. Obtiveram-se correlações significativas nas reduções de absorbãncia com os valores calorimétricos "a", "b" e "h". Essas coordenadas foram as que explicaram melhor as variações ocorridas na decomposição do pigmento.