A New Paclitaxel Formulation Based on Secretome Isolated from Mesenchymal Stem Cells Shows a Significant Cytotoxic Effect on Osteosarcoma Cell Lines.

BACKGROUND: Osteosarcoma (OS) represents a rare cancer with an unfavorable prognosis that needs innovative treatment. The aim was to isolate a secretome from mesenchymal stem cells (MSCs) that are treated with paclitaxel (PTX)-containing microvesicles as a drug delivery system and analyze its cytotoxic effects on OS cell lines (SJSA, MG63, and HOS). METHODS: Three batches of secretome (SECR-1, SECR-2, and SECR-3) were produced from three bone marrow (BM) MSCs samples treated for 24 h with 15 µg/mL of PTX or with a standard medium. The viability of the OS cell lines after 5 days of exposure to SECR-1-2-3 (pure and diluted to 1:2 and 1:4) was analyzed with an MTT assay. The same SECR batches were analyzed with high-performance liquid chromatography (HPLC) and with a nanoparticle tracking assay (NTA). RESULTS: A statistically significant decrease in the viability of all OS cell lines was observed after treatment with SECR-PTX 1-2-3 in a dose-response manner. The NTA analyses showed the presence of nanoparticles (NPs) with a mean size comparable to that of extracellular vesicles (EVs). The HPLC analyses detected the presence of PTX in minimal doses in all SECR batches. CONCLUSIONS: This proof-of-concept study showed that the conditioned medium isolated from MSCs loaded with PTX had a strong cytotoxic effect on OS cell lines, due to the presence of EV and PTX.

Dietary intervention for tertiary prevention in head and neck squamous cell carcinoma survivors: clinical and translational results of a randomized phase II trial.

Background: There is a strong need for preventive approaches to reduce the incidence of recurrence, second cancers, and late toxicities in head and neck squamous cell carcinoma (HNSCC) survivors. We conducted a randomized controlled trial (RCT) to assess a dietary intervention as a non-expensive and non-toxic method of tertiary prevention in HNSCC survivors. Methods: Eligible participants were disease-free patients with HNSCC in follow-up after curative treatments. Subjects were randomized 1:1 to receive a highly monitored dietary intervention plus the Word Cancer Research Fund/American Institute for Cancer Research recommendations for cancer prevention (intervention arm) or standard-of-care recommendations (control arm). The planned sample size for the event-free survival evaluation (primary endpoint) was not reached, and the protocol was amended in order to investigate the clinical (nutritional and quality-of-life questionnaires) and translational study [plasma-circulating food-related microRNAs (miRNAs)] as main endpoints, the results of which are reported herein. Results: One hundred patients were screened, 94 were randomized, and 89 were eligible for intention-to-treat analysis. Median event-free survival was not reached in both arms. After 18 months, nutritional questionnaires showed a significant increase in Recommended Food Score (p = 0.04) in the intervention arm vs. control arm. The frequency of patients with and without a clinically meaningful deterioration or improvement of the C30 global health status in the two study arms was similar. Food-derived circulating miRNAs were identified in plasma samples at baseline, with a significant difference among countries. Conclusion: This RCT represented the first proof-of-principle study, indicating the feasibility of a clinical study based on nutritional and lifestyle interventions in HNSCC survivors. Subjects receiving specific counseling increased the consumption of the recommended foods, but no relevant changes in quality of life were recorded between the two study arms. Food-derived plasma miRNA might be considered promising circulating dietary biomarkers.

Gestational diabetes mellitus yesterday, today and tomorrow: A 13 year italian cohort study.

AIMS: To describe all cases of gestational diabetes mellitus (GDM) managed at the Italian Hospital of San Daniele del Friuli from 2006 to 2018, after the establishment of a dedicated multidisciplinary team. METHODS: Data on mothers, pregnancies, and newborns have been recorded since the team establishment. The associations of maternal, pregnancy, and delivery characteristics with complications of pregnancy and delivery and adverse birth outcomes were assessed. RESULTS: 894 cases of GDM were observed, representing 6.8% of all deliveries. More than 20% of women were non-Italian, 5.3% had a previous macrosomic child, 12.5% previous diabetes or GDM, 27.3% family history of diabetes. On average, women had 4 visits at the clinic; mean glycated hemoglobin was 5.3%; starting body mass index (BMI) 26.2 and weight gain 10.3 kg. Cesarean sections were 21.8%. Pre-eclampsia was the most common pregnancy complication (4.7%). 6.0% of newborns were macrosomic and there were 3 fetal deaths. Only 26.3% of women had a post-partum oral glucose tolerance test. Initial BMI, weight gain, nationality, family history of diabetes or previous diabetes-related pregnancy complications were associated with pregnancy complications or adverse outcomes. CONCLUSIONS: We identified factors to be targeted for preventing GDM complications. Further efforts should be directed at post-partum.

El trabajo en pequeños grupos facilita la enseñanza-aprendizaje de Bioquímica / Work in small groups makes easy the Biochemical teaching and learning

El objetivo de este trabajo fue analizar la nueva propuesta de enseñanza de Bioquímica en la carrera de Medicina, que incluyó cambios en las estrategias de enseñanza-aprendizaje y de evaluación. Las clases expositivas fueron reemplazadas por la Discusión en Pequeños Grupos (DPG), en la que diez alumnos discuten situaciones del proceso salud-enfermedad. Los exámenes parciales individuales fueron reemplazados por la Evaluación en Pequeños Grupos (EPG) con la presentación de situaciones problema para la discusión y el análisis grupal. La información del presente estudio, de abordaje cualitativo, se obtuvo a partir de entrevistas semiestructuradas con docentes y alumnos. Los núcleos de análisis fueron: motivación, relaciones interpersonales, trabajo en grupo, construcción de conocimientos, comunicación, integración teórico-práctica y evaluación. La articulación de la DPG con las demás estrategias didácticas, como Clases de Consolidación, Seminarios Científicos, Trabajos Prácticos de Laboratorio y EPG motivó a docentes y alumnos, permitió la recuperación de conocimientos previos, la búsqueda activa de conocimientos e incentivó las relaciones interpersonales colaborativas y la integración conceptual. De esta forma, la incorporación de estrategias problematizadoras en grupos favoreció los procesos de aprendizaje significativo promoviendo las readecuaciones.

The objective of this work was the analysis of the new biochemistry teaching proposal presented in the Medicine Career. This proposal included changes in the teaching-learning and evaluation strategies. Explanatory lessons were replaced for Discussions in Small Groups (DSG) where groups of ten students discuss different issues related to situations in the health-illness process. At the same time, individual mid-term exams were changed for Evaluations in Small Groups (ESG) with presentation of problematic situations for discussion and group analysis. The qualitative information contained herein was obtained from organized meetings with teachers and students. The data analysis was directed by: motivation, interpersonal relationships, group work, knowledge building, communication, theoretical and practical integration and evaluation. The DSG together with other didactic strategies of the department such as Consolidation Lessons, Scientific Seminars, Laboratory Written Assignments and ESG motivated teachers and students, allowed the recovery of previous knowledge and the active search for it, encouraged the interpersonal relationships and the conceptual integration. In this way, the inclusion of this type of strategies benefited the significant learning processes and promoted changes.

O objetivo de este trabalho foi analisar a nova proposta de ensino de Bioquímica na carreira de Medicina, incluindo as mudanças nas estratégias de ensino-aprendizagem e de avaliação. As aulas expositivas foram substituídas pela Discussão em Pequenos Grupos (DPG), em que dez alunos discutem situações do processo saúde-doença. As provas parciais individuais foram substituías pela Avaliação em Pequenos Grupos (APG) com a apresentação de situações problema para a discussão e a análise grupal. As informações para este estudo, de abordagem qualitativa, foram obtidas a partir de entrevistas semi-estruturadas com docentes e alunos. Os núcleos de análise foram: a motivação, as relações interpessoais, o trabalho em grupo, a construção de conhecimentos, a comunicação, a integração teórico-prática e a avaliação. A articulação da DPG com as demais estratégias didáticas, como as Aulas de Consolidação, Seminários Científicos, Trabalhos Práticos de Laboratório e APG motivou docentes e alunos, permitiu a recuperação de conhecimentos prévios, a busca ativa de conhecimentos e incentivou as relações interpessoais colaborativas e a integração conceitual. Desta forma, a incorporação de estratégias problematizadoras em grupos, tem favorecido os processos de aprendizagem significativa promovendo as readequações.