Roles of the hox proteins in cancer invasion and metastasis

Invasion and metastasis correspond to the foremost cause of cancer-related death, and the molecular networks behind these two processes are extremely complex and dependent on the intra-and extracellular conditions along with the prime of the premetastatic niche. Currently, several studies suggest an association between the levels of HOX genes expression and cancer cell invasion and metastasis, which favour the formation of novel tumour masses. The deregulation of HOX genes by HMGA2/TET1 signalling and the regulatory effect of noncoding RNAs generated by the HOX loci can also promote invasion and metastasis, interfering with the expression of HOX genes or other genes relevant to these processes. In this review, we present five molecular mechanisms of HOX deregulation by which the HOX clusters products may affect invasion and metastatic processes in solid tumours.The work was financed by FEDER (Fundo Europeu de Desenvolvimento Regional) funds through the COMPETE 2020 Operational Programme for Competitiveness and Internationalisa-tion (POCI), Portugal 2020, and by Portuguese funds through FCT (Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior) in the framework of the project POCI-01-0145-FEDER-030562 (PTDC/BTM-TEC/30562/2017). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed

Morphology and behavior of the early stages of the skipper, Urbanus esmeraldus, on Urera baccifera, an ant-visited host plant

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)The Neotropical genus Urbanus (Hubner) (Lepidoptera: Hesperiidae) contains around 34 described species, and is widely distributed from the extreme southern United States to Argentina. Here, we describe the larval morphology and behavior of Urbanus esmeraldus (Hubner)(Hesperiidae) in Urera baccifera (Urticaceae), a plant producing food rewards and fleshy fruits that attract ants (including predacious species) in a Brazilian forest. Larvae pass through five instars and construct two kinds of leaf shelters. Experiments with ejected fecal pellets showed that these can serve as cues to ground-dwelling ants that climb onto host plants and potentially attack the larvae. Manipulation with pellets placed at different distances suggests that ejection behavior decreases larval vulnerability to ant predation. Larval preference for mature leaves may be related with increased predation risk at ant-visited young leaves. The study shows that a combination of natural history and experimental data can help understand the life history of a butterfly using a plant with high predation risk.12Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundo de Apoio ao Ensino, a Pesquisa e a Extensao (FAEPEX)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)FAPESP [00/01484-1, 04/05269-9]FAPESP [98/05101-8

Complex Polysaccharide-Based Nanocomposites for Oral Insulin Delivery

Polyelectrolyte nanocomposites rarely reach a stable state and aggregation often occurs. Here, we report the synthesis of nanocomposites for the oral delivery of insulin composed of alginate, dextran sulfate, poly-(ethylene glycol) 4000, poloxamer 188, chitosan, and bovine serum albumin. The nanocomposites were obtained by Ca2+-induced gelation of alginate followed by an electrostatic-interaction process among the polyelectrolytes. Chitosan seemed to be essential for the final size of the nanocomposites and there was an optimal content that led to the synthesis of nanocomposites of 400–600 nm hydrodynamic size. The enhanced stability of the synthesized nanocomposites was assessed with LUMiSizer after synthesis. Nanocomposite stability over time and under variations of ionic strength and pH were assessed with dynamic light scattering. The rounded shapes of nanocomposites were confirmed by scanning electron microscopy. After loading with insulin, analysis by HPLC revealed complete drug release under physiologically simulated conditions

Síndrome coronária aguda de origem paradoxal

We describe a rare case of acute myocardial infarction secondary to paradoxical embolism complicating acute pulmonary embolism. A 44-year-old woman presented to the emergency department with chest pain. The physical examination was unremarkable except for oxygen saturation of 75%, and the electrocardiogram showed ST-segment elevation in the inferior leads. Urgent coronary angiography showed a distal occlusion of the right coronary artery and multiple thrombi were aspirated. Despite relief of chest pain and electrocardiogram normalization, her oxygen saturation remained low (90%) with high-flow oxygen by mask. The transthoracic echocardiogram showed a mass in the left atrium and dilatation of the right chambers, while the transesophageal echocardiogram showed a thrombus attached to the interatrial septum in the region of the foramen ovale. Color flow imaging was consistent with a patent foramen ovale. Thoracic computed tomography angiography documented thrombi in both branches of the pulmonary trunk. After five days on anticoagulation, the patient underwent surgical foramen ovale closure

IS element IS16 as a molecular screening tool to identify hospital-associated strains of Enterococcus faecium

<p>Abstract</p> <p>Background</p> <p>Hospital strains of <it>Enterococcus faecium </it>could be characterized and typed by various molecular methods (MLST, AFLP, MLVA) and allocated to a distinct clonal complex known as MLST CC17. However, these techniques are laborious, time-consuming and cost-intensive. Our aim was to identify hospital <it>E. faecium </it>strains and differentiate them from colonizing and animal variants by a simple, inexpensive and reliable PCR-based screening assay. We describe here performance and predictive value of a single PCR detecting the insertion element, IS<it>16</it>, to identify hospital <it>E. faecium </it>isolates within a collection of 260 strains of hospital, animal and human commensal origins.</p> <p>Methods</p> <p>Specific primers were selected amplifying a 547-bp fragment of IS<it>16</it>. Presence of IS<it>16 </it>was determined by PCR screenings among the 260 <it>E. faecium </it>isolates. Distribution of IS<it>16 </it>was compared with a prevalence of commonly used markers for hospital strains, <it>esp </it>and <it>hyl</it>_<it>Efm</it>. All isolates were typed by MLST and partly by PFGE. Location of IS<it>16 </it>was analysed by Southern hybridization of plasmid and chromosomal DNA.</p> <p>Results</p> <p>IS<it>16 </it>was exclusively distributed only among 155 invasive strains belonging to the clonal complex of hospital-associated strains ("CC17"; 28 MLST types) and various vancomycin resistance genotypes (<it>van</it>A/B/negative). The five invasive IS<it>16</it>-negative strains did not belong to the clonal complex of hospital-associated strains (CC17). IS<it>16 </it>was absent in all but three isolates from 100 livestock, food-associated and human commensal strains ("non-CC17"; 64 MLST types). The three IS<it>16</it>-positive human commensal isolates revealed MLST types belonging to the clonal complex of hospital-associated strains (CC17). The values predicting a hospital-associated strain ("CC17") deduced from presence and absence of IS<it>16 </it>was 100% and thus superior to screening for the presence of <it>esp </it>(66%) and/or <it>hyl</it>_{<it>Efm </it>}(46%). Southern hybridizations revealed chromosomal as well as plasmid localization of IS<it>16</it>.</p> <p>Conclusions</p> <p>This simple screening assay for insertion element IS<it>16 </it>is capable of differentiating hospital-associated from human commensal, livestock- and food-associated <it>E. faecium </it>strains and thus allows predicting the epidemic strengths or supposed pathogenic potential of a given <it>E. faecium </it>isolate identified within the nosocomial setting.</p

IS element IS16 as a molecular screening tool to identify hospital-associated strains of Enterococcus faecium

<p>Abstract</p> <p>Background</p> <p>Hospital strains of <it>Enterococcus faecium </it>could be characterized and typed by various molecular methods (MLST, AFLP, MLVA) and allocated to a distinct clonal complex known as MLST CC17. However, these techniques are laborious, time-consuming and cost-intensive. Our aim was to identify hospital <it>E. faecium </it>strains and differentiate them from colonizing and animal variants by a simple, inexpensive and reliable PCR-based screening assay. We describe here performance and predictive value of a single PCR detecting the insertion element, IS<it>16</it>, to identify hospital <it>E. faecium </it>isolates within a collection of 260 strains of hospital, animal and human commensal origins.</p> <p>Methods</p> <p>Specific primers were selected amplifying a 547-bp fragment of IS<it>16</it>. Presence of IS<it>16 </it>was determined by PCR screenings among the 260 <it>E. faecium </it>isolates. Distribution of IS<it>16 </it>was compared with a prevalence of commonly used markers for hospital strains, <it>esp </it>and <it>hyl</it>_<it>Efm</it>. All isolates were typed by MLST and partly by PFGE. Location of IS<it>16 </it>was analysed by Southern hybridization of plasmid and chromosomal DNA.</p> <p>Results</p> <p>IS<it>16 </it>was exclusively distributed only among 155 invasive strains belonging to the clonal complex of hospital-associated strains ("CC17"; 28 MLST types) and various vancomycin resistance genotypes (<it>van</it>A/B/negative). The five invasive IS<it>16</it>-negative strains did not belong to the clonal complex of hospital-associated strains (CC17). IS<it>16 </it>was absent in all but three isolates from 100 livestock, food-associated and human commensal strains ("non-CC17"; 64 MLST types). The three IS<it>16</it>-positive human commensal isolates revealed MLST types belonging to the clonal complex of hospital-associated strains (CC17). The values predicting a hospital-associated strain ("CC17") deduced from presence and absence of IS<it>16 </it>was 100% and thus superior to screening for the presence of <it>esp </it>(66%) and/or <it>hyl</it>_{<it>Efm </it>}(46%). Southern hybridizations revealed chromosomal as well as plasmid localization of IS<it>16</it>.</p> <p>Conclusions</p> <p>This simple screening assay for insertion element IS<it>16 </it>is capable of differentiating hospital-associated from human commensal, livestock- and food-associated <it>E. faecium </it>strains and thus allows predicting the epidemic strengths or supposed pathogenic potential of a given <it>E. faecium </it>isolate identified within the nosocomial setting.</p