Current approaches in tissue engineering-based nanotherapeutics for osteosarcoma treatment.

Osteosarcoma (OS) is a malignant bone neoplasm plagued by poor prognosis. Major treatment strategies include chemotherapy, radiotherapy, and surgery. Chemotherapy to treat OS has severe adverse effects due to systemic toxicity to healthy cells. A possible way to overcome the limitation is to utilize nanotechnology. Nanotherapeutics is an emerging approach in treating OS using nanoparticulate drug delivery systems. Surgical resection of OS leaves a critical bone defect requiring medical intervention. Recently, tissue engineered scaffolds have been reported to provide physical support to bone defects and aid multimodal treatment of OS. These scaffolds loaded with nanoparticulate delivery systems could also actively repress tumor growth and aid new bone formation. The rapid developments in nanotherapeutics and bone tissue engineering have paved the way for improved treatment efficacy for OS-related bone defects. This review focuses on current bifunctional nanomaterials-based tissue engineered (NTE) scaffolds that use novel approaches such as magnetic hyperthermia, photodynamic therapy, photothermal therapy, bioceramic and polymeric nanotherapeutics against OS. With further optimization and screening, NTE scaffolds could meet clinical applications for treating OS patients.

Medical education from the point of view of medical students: Results from four participatory Delphi panels in Quito, Ecuador.

BACKGROUND: Medical curricula have historically been designed in a top-down approach, usually excluding students. While Delphi panels have been used as a tool for medical education curricula design, none have been conducted in Ecuador. In addition, no such approach has ever included students both as panelists and researchers. MATERIAL AND METHODS: Four Delphi panels were developed and conducted using a participatory approach that allowed medical students to take part both as expert panelists and researchers: specifically, students developed the questionnaire and conducted a qualitative synthesis. Questionnaire responses were anonymized and dispatched online to panelists. The information was organized and collected to develop the qualitative syntheses and prepare the final statements. RESULTS: Thirty-two medical students participated between February and May 2018. A total of 32 questions were developed, corresponding to five different categories. For some questions, consensus was reached; for other questions, general statements were obtained.Discussion and conclusion: Developing the questionnaire, responding to it and analyzing the answers allowed students to raise significant concerns regarding medical education topics proposing relevant policy and curricula change. Participatory Delphi panels can be an efficient tool to obtain organized feedback, improve student class involvement, and promote research skills.

miR-590-3p inhibits proliferation and promotes apoptosis by targeting activating transcription factor 3 in human breast cancer cells.

We previously reported that ATF3 and Runx2 are involved in breast cancer progression and bone metastasis. The expression of these genes can be controlled by post-transcriptional regulators such as microRNAs (miRNAs). In this study, we identified and validated the functional role of miR-590-3p in human breast cancer cells (MDA-MB231). There was an inverse correlation between the expression of miR-590-3p and its putative target genes, ATF3 and Runx2 in these cells. Overexpression of miR-590-3p decreased the expression of ATF3 and Runx2 at the mRNA and protein levels in MDA-MB231 cells. Luciferase reporter assay identified a direct interaction of 3' UTRs of ATF3 and Runx2 with miR-590-3p in these cells. Overexpression of miR-590-3p also decreased proliferation and increased apoptosis of breast cancer cells. Based on our results, we suggest that miR-590-3p might have potential clinical applications towards controlling breast cancer progression and bone metastasis.

Runx2: Structure, function, and phosphorylation in osteoblast differentiation.

Runx2 is a master transcription factor for osteogenesis. The most important phenomenon that makes this protein a master regulator for osteogenesis is its structural integrity. In response to various stimuli, the domains in Runx2 interact with several proteins and regulate a number of cellular events via posttranslational modifications. Hence, in this review we summarized the structural integrity of Runx2 and its posttranslational modifications, especially the phosphorylation responsible for either stimulation or inhibition of its regulatory role in osteogenesis.

A feedback expression of microRNA-590 and activating transcription factor-3 in human breast cancer cells.

MicroRNAs (miRNAs) are small non coding RNA molecules (∼ 23 nt) that are capable of regulating several physiological and pathological processes by targeting mRNAs post transcriptionally, and miRNAs are also known to be regulated by their own target gene(s) in a feedback manner. In this study, we analysed the expression of miRNAs (pre-mir-93, pre-mir-20b, pre-mir-520 c, pre-mir-143, pre-mir-154 and pre-mir-590) by body map, an in silico method and by qRT-PCR in MDA-MB231 (highly invasive and metastatic in nature), and MCF-7 (poor invasive and metastatic in nature) cells. These miRNAs were down regulated in MDA-MB231 cells, and among these, miR-590 was found to putatively target activating transcription factor-3 (ATF-3), a stress response gene. ATF-3 expression level was significantly increased in MDA-MB231 cells and inhibition of ATF-3 expression in these cells increased the expression of pre-mir-590. Thus, these results suggest that there is a negative feedback expression of pre-mir-590 and its putative target gene, ATF-3 in human breast cancer cells.

Regulation of breast cancer and bone metastasis by microRNAs.

Breast cancer progression including bone metastasis is a complex process involving numerous changes in gene expression and function. MicroRNAs (miRNAs) are small endogenous noncoding RNAs that regulate gene expression by targeting protein-coding mRNAs posttranscriptionally, often affecting a number of gene targets simultaneously. Alteration in expression of miRNAs is common in human breast cancer, possessing with either oncogenic or tumor suppressive activity. The expression and the functional role of several miRNAs (miR-206, miR-31, miR-27a/b, miR-21, miR-92a, miR-205, miR-125a/b, miR-10b, miR-155, miR-146a/b, miR-335, miR-204, miR-211, miR-7, miR-22, miR-126, and miR-17) in breast cancer has been identified. In this review we summarize the experimentally validated targets of up- and downregulated miRNAs and their regulation in breast cancer and bone metastasis for diagnostic and therapeutic purposes.

Cultivation of the third-stage larvae of Necator americanus in vitro.

When filariform larvae of Necator americanus, enclosed within the second sheath, were cultured in various semi-defined media, the best larval development was achieved in Waymouth's MB 752/1 with 20% foetal calf serum (FCS). In this medium, most of the filariform larvae cast off the second sheath and developed into third-stage larvae with provisional buccal capsules and some larvae developed further; 26% were fourth stage after 49 days of culture. Of several supplements tested, only FCS supported such development and no further development occurred if the medium was further supplemented with human red blood cells, liver extract, intestinal extract or tryptose phosphate broth. Larval development stopped at or before early third stage in Eagle's Basal Medium, F-12, NCTC 135 and L-15, even when these media were supplemented with FCS.