Endometrial Cancer Spheres Show Cancer Stem Cells Phenotype and Preference for Oxidative Metabolism

This study aimed to characterize endometrial cancer regarding cancer stem cells (CSC) markers, regulatory and differentiation pathways, tumorigenicity and glucose metabolism. Endometrial cancer cell line ECC1 was submitted to sphere forming protocols. The first spheres generation (ES1) was cultured in adherent conditions (G1). This procedure was repeated and was obtained generations of spheres (ES1, ES2 and ES3) and spheres-derived cells in adherent conditions (G1, G2 and G3). Populations were characterized regarding CD133, CD24, CD44, aldehyde dehydrogenase (ALDH), hormonal receptors, HER2, P53 and β-catenin, fluorine-18 fluorodeoxyglucose ([18F]FDG) uptake and metabolism by NMR spectroscopy. An heterotopic model evaluated differential tumor growth. The spheres self-renewal was higher in ES3. The putative CSC markers CD133, CD44 and ALDH expression were higher in spheres. The expression of estrogen receptor (ER)α and P53 decreased in spheres, ERβ and progesterone receptor had no significant changes and β-catenin showed a tendency to increase. There was a higher 18F-FDG uptake in spheres, which also showed a lower lactate production and an oxidative cytosol status. The tumorigenesis in vivo showed an earlier growth of tumours derived from ES3. Endometrial spheres presented self-renewal and differentiation capacity, expressed CSC markers and an undifferentiated phenotype, showing preference for oxidative metabolism.info:eu-repo/semantics/publishedVersio

Granular cell tumor presenting as a tongue nodule: two case reports

<p>Abstract</p> <p>Introduction</p> <p>Granular cell tumor is an uncommon neoplasm that can occur in any part of the body, including the orofacial region. The tumor is usually benign, but there are reports of cases in which the tumor shows a locally aggressive behavior, malignancy, and distant metastases. The most widely accepted hypothesis is that granular cell tumor arises from the altered metabolism of Schwann cells. The tumor is typically asymptomatic and appears as a nodule that does not exceed 3 cm.</p> <p>Case presentation</p> <p>In case 1, a 26-year-old Caucasian man was seen at the Oral Medicine out-patient clinic of the São José dos Campos Dental School, Universidade Estadual Paulista, with a 'small blister on the tongue', which he had noted approximately three years ago. The nodule was located on the dorsum of the tongue, measured about 1.5 cm in diameter, and was not tender to palpation. Treatment consisted of an excisional biopsy performed on the basis of the diagnostic hypothesis of granular cell tumor, which was confirmed by microscopic analysis. In case 2, a 31-year-old Caucasian woman attended the out-patient clinic of the São José dos Campos Dental School, Universidade Estadual Paulista, with a five-year history of a 'painful lump on the tongue'. Intra-oral examination revealed the presence of a nodular lesion measuring approximately 0.8 cm in diameter, which was located deep in the submucosa of the right lateral margin of the tongue. Treatment consisted of an excisional biopsy performed on the basis of the differential diagnosis of neurofibroma and granular cell tumor. Microscopic analysis defined the final diagnosis of granular cell tumor.</p> <p>Conclusions</p> <p>Granular cell tumor is an uncommon tumor that must be carefully diagnosed and treated correctly.</p

Адаптация гидравлической модели водостока к бассейнам рек Дунай и Днестр

Гидравлическая модель водостока адаптирована к бассейну рек Дунай и Днестр. По данным орографии, атмосферных осадках или поверхностном стоке она позволяет рассчитывать объемы, расходы и уровни воды с пространственным разрешением 1 км. В модели возможно использование данные об экосистемах на земной поверхности, типах почвы. По данным наблюдений стока оценены среднемесячные величины расходов рек, которые соответствуют наблюдениям, что позволяет применять модель в дальнейших оценках стока, наносов и т.д.Hydraulic model of water inflow is adapted to the Danube and the Dniester rivers basin. According to the orography, precipitation and surface inflow data it permits to calculate water volumes, discharges and levels with spatial resolution 1 km. It is possible to use the data on ecosystems on the ground surface, types of soil in the model. According to the observations data of the inflow the average monthly values of river discharges corresponding to the observations are estimated. It permits to apply the model in the further estimations of inflow, alluvia e t.c

Transcription of toll-like receptors 2, 3, 4 and 9, FoxP3 and Th17 cytokines in a susceptible experimental model of canine Leishmania infantum infection

Canine leishmaniosis (CanL) due to Leishmania infantum is a chronic zoonotic systemic disease resulting from complex interactions between protozoa and the canine immune system. Toll-like receptors (TLRs) are essential components of the innate immune system and facilitate the early detection of many infections. However, the role of TLRs in CanL remains unknown and information describing TLR transcription during infection is extremely scarce. The aim of this research project was to investigate the impact of L. infantum infection on canine TLR transcription using a susceptible model. The objectives of this study were to evaluate transcription of TLRs 2, 3, 4 and 9 by means of quantitative reverse transcription polymerase chain reaction (qRT-PCR) in skin, spleen, lymph node and liver in the presence or absence of experimental L. infantum infection in Beagle dogs. These findings were compared with clinical and serological data, parasite densities in infected tissues and transcription of IL-17, IL-22 and FoxP3 in different tissues in non-infected dogs (n = 10), and at six months (n = 24) and 15 months (n = 7) post infection. Results revealed significant down regulation of transcription with disease progression in lymph node samples for TLR3, TLR4, TLR9, IL-17, IL-22 and FoxP3. In spleen samples, significant down regulation of transcription was seen in TLR4 and IL-22 when both infected groups were compared with controls. In liver samples, down regulation of transcription was evident with disease progression for IL-22. In the skin, upregulation was seen only for TLR9 and FoxP3 in the early stages of infection. Subtle changes or down regulation in TLR transcription, Th17 cytokines and FoxP3 are indicative of the silent establishment of infection that Leishmania is renowned for. These observations provide new insights about TLR transcription, Th17 cytokines and Foxp3 in the liver, spleen, lymph node and skin in CanL and highlight possible markers of disease susceptibility in this model

Nanostructured Systems Containing Rutin: In Vitro Antioxidant Activity and Photostability Studies

The improvement of the rutin photostability and its prolonged in vitro antioxidant activity were studied by means of its association with nanostructured aqueous dispersions. Rutin-loaded nanocapsules and rutin-loaded nanoemulsion showed mean particle size of 124.30 ± 2.06 and 124.17 ± 1.79, respectively, polydispersity index below 0.20, negative zeta potential, and encapsulation efficiency close to 100%. The in vitro antioxidant activity was evaluated by the formation of free radical ·OH after the exposure of hydrogen peroxide to a UV irradiation system. Rutin-loaded nanostructures showed lower rutin decay rates [(6.1 ± 0.6) 10−3 and (5.1 ± 0.4) 10−3 for nanocapsules and nanoemulsion, respectively] compared to the ethanolic solution [(35.0 ± 3.7) 10−3 min−1] and exposed solution [(40.1 ± 1.7) 10−3 min−1] as well as compared to exposed nanostructured dispersions [(19.5 ± 0.5) 10−3 and (26.6 ± 2.6) 10−3, for nanocapsules and nanoemulsion, respectively]. The presence of the polymeric layer in nanocapsules was fundamental to obtain a prolonged antioxidant activity, even if the mathematical modeling of the in vitro release profiles showed high adsorption of rutin to the particle/droplet surface for both formulations. Rutin-loaded nanostructures represent alternatives to the development of innovative nanomedicines

Inhibition of PbGP43 expression may suggest that gp43 is a virulence factor in Paracoccidioides brasiliensis

ABSTARCT: Glycoprotein gp43 is an immunodominant diagnostic antigen for paracoccidioidomycosis caused by Paracoccidioides brasiliensis. It is abundantly secreted in isolates such as Pb339. It is structurally related to beta-1,3-exoglucanases, however inactive. Its function in fungal biology is unknown, but it elicits humoral, innate and protective cellular immune responses; it binds to extracellular matrix-associated proteins. In this study we applied an antisense RNA (aRNA) technology and Agrobacterium tumefaciens-mediated transformation to generate mitotically stable PbGP43 mutants (PbGP43 aRNA) derived from wild type Pb339 to study its role in P. brasiliensis biology and during infection. Control PbEV was transformed with empty vector. Growth curve, cell vitality and morphology of PbGP43 aRNA mutants were indistinguishable from those of controls. PbGP43 expression was reduced 80-85% in mutants 1 and 2, as determined by real time PCR, correlating with a massive decrease in gp43 expression. This was shown by immunoblotting of culture supernatants revealed with anti-gp43 mouse monoclonal and rabbit polyclonal antibodies, and also by affinity-ligand assays of extracellular molecules with laminin and fibronectin. In vitro, there was significantly increased TNF-α production and reduced yeast recovery when PbGP43 aRNA1 was exposed to IFN-γ-stimulated macrophages, suggesting reduced binding/uptake and/or increased killing. In vivo, fungal burden in lungs of BALB/c mice infected with silenced mutant was negligible and associated with decreased lung ΙΛ-10 and IL-6. Therefore, our results correlated low gp43 expression with lower pathogenicity in mice, but that will be definitely proven when PbGP43 knockouts become available.

A large outbreak of Legionnaires’ Disease in an industrial town in Portugal

Background We describe the investigation and control of an outbreak of Legionnaires’ disease in Portugal in October, November and December 2014. Methods Confirmed cases were individuals with pneumonia, laboratory evidence of Legionella pneumophila serogroup 1 and exposure, by residence, occupational or leisure to the affected municipalities. 49 possible sources were reduced to four potential sources, all industries with wet cooling system, following risk assessment. We geo-referenced cases’ residences and the location of cooling towers defining four study areas 10 km buffer centered on each cooling tower system. We compared the number of cases with expected numbers, calculated from the outbreak's attack rates applied to 2011 census population. Using Stones’ Test, we tested observed to expected ratios for decline in risk, with distance up to 10 km four directions. Isolates of Legionella pneumophila were compared using molecular methods. Results We identified 403 cases, 377 of which were confirmed, 14 patients died. Patients became ill between 14 October and 2 December. A NE wind and thermal inversion were recorded during the estimated period of exposure. Disease risk was highest in people living south west from all of the industries identified and decreased with distance (p < 0.001). 71 clinical isolates demonstrated an identical SBT profile to an isolate from a cooling tower. Whole genome sequencing identified an unusual L. pneumophila subsp. fraseri serogroup 1 as the outbreak causative strain, and confirmed isolates’ relatedness. Conclusions Industrial wet cooling systems, bacteria with enhanced survival characteristics and a combination of climatic conditions contributed to the second largest outbreak of Legionnaires’ disease recorded internationally.info:eu-repo/semantics/publishedVersio