Dental pulp stem cells and Bonelike® for bone regeneration in ovine model

Development of synthetic bone substitutes has arisen as a major research interest in the need to find an alternative to autologous bone grafts. Using an ovine model, the present pre-clinical study presents a synthetic bone graft (Bonelike®) in combination with a cellular system as an alternative for the regeneration of non-critical defects. The association of biomaterials and cell-based therapies is a promising strategy for bone tissue engineering. Mesenchymal stem cells (MSCs) from human dental pulp have demonstrated both in vitro and in vivo to interact with diverse biomaterial systems and promote mineral deposition, aiming at the reconstruction of osseous defects. Moreover, these cells can be found and isolated from many species. Non-critical bone defects were treated with Bonelike® with or without MSCs obtained from the human dental pulp. Results showed that Bonelike® and MSCs treated defects showed improved bone regeneration compared with the defects treated with Bonelike® alone. Also, it was observed that the biomaterial matrix was reabsorbed and gradually replaced by new bone during the healing process. We therefore propose this combination as an efficient binomial strategy that promotes bone growth and vascularization in non-critical bone defects.This research was supported by Programa Operacional Regional do Norte (ON.2 – O Novo Norte), QREN, FEDER with the project ‘iBone Therapies: Terapias inovadoras para a regeneração óssea’, ref. NORTE-01-0247-FEDER-003262, and by the programme COMPETE – Programa Operacional Factores de Competitividade, Projects PEst-OE/AGR/UI0211/2011 and PEst-C/EME/UI0285/2013 funding from FCT. This research was also supported by Programa Operacional Competitividade e Internacionalizac¸~ao (P2020), Fundos Europeus Estruturais e de Investimento (FEEI) and FCT with the project ‘BioMate—A novel bio-manufacturing system to produce bioactive scaffolds for tissue engineering’ with reference PTDC/EMS-SIS/7032/2014 and by COMPETE 2020, from ANI—Projectos ID&T Empresas em Copromoção Programas Operacionais POCI, by the project ‘insitu.Biomas - Reinvent biomanufacturing systems by using an usability approach for in situ clinic temporary implants fabrication’ with the reference POCI-01-0247-FEDER-017771. The research was also supported by the research project ‘BEPIM III –Microdispositivos me´dicos com capacidades osteintegradoras por micoPIM’, with the reference POCI-01-0247-FEDER-017935, from Fundo Europeu de Desenvolvimento Regional (FEDER), by the Programa Operacional da Competitividade & Internacionalização. Ana Rita Caseiro (SFRH/BD/101174/2014) acknowledges FCT, for financial support

CDK7 Inhibition Suppresses Super-Enhancer-Linked Oncogenic Transcription in MYCN-Driven Cancer

The MYC oncoproteins are thought to stimulate tumor cell growth and proliferation through amplification of gene transcription, a mechanism that has thwarted most efforts to inhibit MYC function as potential cancer therapy. Using a covalent inhibitor of cyclin-dependent kinase 7 (CDK7) to disrupt the transcription of amplified MYCN in neuroblastoma cells, we demonstrate downregulation of the oncoprotein with consequent massive suppression of MYCN-driven global transcriptional amplification. This response translated to significant tumor regression in a mouse model of high-risk neuroblastoma, without the introduction of systemic toxicity. The striking treatment selectivity of MYCN-overexpressing cells correlated with preferential downregulation of super-enhancer-associated genes, including MYCN and other known oncogenic drivers in neuroblastoma. These results indicate that CDK7 inhibition, by selectively targeting the mechanisms that promote global transcriptional amplification in tumor cells, may be useful therapy for cancers that are driven by MYC family oncoproteins.United States. National Institutes of Health (R01CA148688)United States. National Institutes of Health (R01CA148688S1)United States. National Institutes of Health (R01CA179483-01)United States. National Institutes of Health (CA109901)United States. National Institutes of Health (HG002668)United States. National Institutes of Health (R21HG006778)American Cancer Society (RSG-12-247-TBG)United States. Department of Defense (PR120741A)Friends for Life Neuroblastoma Foundatio

Is nonangiogenesis a novel pathway for cancer progression? A study using 3-dimensional tumour reconstructions

The nonangiogenic lung tumour is characterized by neoplastic cells co-opting the pre-existent vasculature and filling the alveoli space. 3-Dimensional reconstruction of the tumour reveals that this particular tumour progresses without neovascularization and there is no major destruction of the lung's architectural integrity

Produção de lenha na região de Iranduba e Manacapuru - Amazonas: Acacia mangium e Acacia auriculiformis.

Importância energética da lenha. Pólo oleiro de Iranduba e Manacapuru. Biomassa, fator de empilhamento, densidade e teor de umidade. Estimativa da produção. Rendimento das espécies na olaria.bitstream/CPAA-2009-09/10581/1/circ_tec16.pd

Phenotypic characterization and identification of bacterial isolates from smoked fish

This study aimed to phenotypically characterize and identify bacterial isolates from smoked fish. From the seven morphologically different bacterial colonies, four of them were identified using selective/differential media. The two isolates belong to genus Pseudomonas while the remaining two were confirmed under genus Staphylococcus. Results of gram-staining, motility and selected biochemical and physiological tests supported the identity of the four isolates. Pseudomonas isolates were found resistant to 30 µg tetracycline while Staphylococcus isolates were intermediate to susceptible on the said antibiotics. Unhygienic preparation of the smoked fish could be the possible reason for the product contamination. Keywords: Smoked fish, phenotypic characterization, biochemical test, physiological test, antibiotic susceptibilit

Copper sulfate-resistant bacteria isolated from Blue Soil Hills, Sagada, Mountain Province, Philippines

The objective of this study was to isolate copper sulfate-resistant bacteria in Blue Soil Hills, Sagada, Mountain, Province, Philippines. Three distinct bacterial colonies were isolated from the soil sample. The isolates were different from one another based upon colonial characteristics and growth patterns in solid and liquid medium. All three bacteria were gram-positive and were able to grow in medium supplemented with various concentrations of copper sulfate. More luxurious growth was observed in medium with highest supplementation (333.33 ppm). The isolated bacteria could be potential bioremediation agents in soil and water heavily contaminated with copper.        Keywords: Copper sulfate, bioremediation, Blue Soil Hills, Sagada, Mountain Provinc

Comparative Genomics Reveals Two Novel RNAi Factors in Trypanosoma brucei and Provides Insight into the Core Machinery

The introduction ten years ago of RNA interference (RNAi) as a tool for molecular exploration in Trypanosoma brucei has led to a surge in our understanding of the pathogenesis and biology of this human parasite. In particular, a genome-wide RNAi screen has recently been combined with next-generation Illumina sequencing to expose catalogues of genes associated with loss of fitness in distinct developmental stages. At present, this technology is restricted to RNAi-positive protozoan parasites, which excludes T. cruzi, Leishmania major, and Plasmodium falciparum. Therefore, elucidating the mechanism of RNAi and identifying the essential components of the pathway is fundamental for improving RNAi efficiency in T. brucei and for transferring the RNAi tool to RNAi-deficient pathogens. Here we used comparative genomics of RNAi-positive and -negative trypanosomatid protozoans to identify the repertoire of factors in T. brucei. In addition to the previously characterized Argonaute 1 (AGO1) protein and the cytoplasmic and nuclear Dicers, TbDCL1 and TbDCL2, respectively, we identified the RNA Interference Factors 4 and 5 (TbRIF4 and TbRIF5). TbRIF4 is a 3′-5′ exonuclease of the DnaQ superfamily and plays a critical role in the conversion of duplex siRNAs to the single-stranded form, thus generating a TbAGO1-siRNA complex required for target-specific cleavage. TbRIF5 is essential for cytoplasmic RNAi and appears to act as a TbDCL1 cofactor. The availability of the core RNAi machinery in T. brucei provides a platform to gain mechanistic insights in this ancient eukaryote and to identify the minimal set of components required to reconstitute RNAi in RNAi-deficient parasites

Angiogenesis extent and macrophage density increase simultaneously with pathological progression in B-cell non-Hodgkin's lymphomas

Node biopsies of 30 benign lymphadenopathies and 71 B-cell non-Hodgkin's lymphomas (B-NHLs) were investigated for microvessel and macrophage counts using immunohistochemistry and morphometric analysis. Both counts were significantly higher in B-NHL. Moreover, when these were grouped into low-grade and high-grade lymphomas, according to the Kiel classification and Working Formulation (WF), statistically significant higher counts were found in the high-grade tumours. Immunohistochemistry and electron microscopy revealed a close spatial association between microvessels and macrophages. Overall, the results suggest that, in analogy to what has already been shown in solid tumours, angiogenesis occurring in B-NHLs increases with tumour progression, and that macrophages promote the induction of angiogenesis via the release of their angiogenic factors. © 1999 Cancer Research Campaig