miR-210 and miR-152 as Biomarkers by Liquid Biopsy in Invasive Ductal Carcinoma.

Detecting circulating microRNAs (miRNAs; miRs) by means of liquid biopsy is an important tool for the early diagnosis and prognosis of breast cancer (BC). We aimed to identify and validate miR-210 and miR-152 as non-invasive circulating biomarkers, for the diagnosis and staging of BC patients, confirming their involvement in tumor angiogenesis. METHODS: RT-qPCR was performed and MiRNA expression analysis was obtained from plasma and fragments of BC and benign breast condition (BBC) women patients, plus healthy subjects. Additionally, the immunohistochemistry technique was carried out to analyze the expression of target proteins. RESULTS: Tumor fragments showed increased expression of oncomiR-210 and decreased expression of miR-152 tumoral suppressor. Both miRNAs were increased in plasma samples from BC patients. The receiver operating characteristic (ROC) curve analysis revealed that only the expression of oncomiR-210 in tissue samples and only the expression of the miR-152 suppressor in plasma have the appropriate sensitivity and specificity for use as differential biomarkers between early/intermediate and advanced stages of BC patients. In addition, there was an increase in the expression of hypoxia-inducible factor 1-alpha (HIF-1α), insulin-like growth factor 1 receptor (IGF-1R), and vascular endothelial growth factor (VEGF) in BC patients. On the contrary, a decrease in Von Hippel-Lindau (VHL) protein expression was observed. CONCLUSIONS: This study showed that increased levels of miR-210 and decreased levels of miR152, in addition to the expressions of their target proteins, could indicate, respectively, the oncogenic and tumor suppressive role of these miRNAs in fragments. Both miRNAs are potential diagnostic biomarkers for BC by liquid biopsy. In addition, miR-152 proved to be a promising biomarker for disease staging.

Melatonin Treatment Combined with TGF-ß Silencing Inhibits Epithelial- Mesenchymal Transition in CF41 Canine Mammary Cancer Cell Line.

BACKGROUND: Mammary cancer is the most prevalent type of cancer in female dogs. The main cause of mortality is the occurrence of metastasis. The metastatic process is complex and involves the Epithelial- Mesenchymal Transition (EMT), which can be activated by Transforming Growth Factor beta (TGF-ß) and involves changes in cellular phenotype, as well as, in the expression of proteins such as E-cadherin, N-cadherin, vimentin and claudin-7. Melatonin is a hormone with oncostatic and anti-metastatic properties and appears to participate in the TGF-ß pathway. Thus, the present work aimed to evaluate the expression of EMT markers, E-cadherin, N-cadherin, vimentin and claudin-7, as well as, the cell migration of the canine mammary cancer cell line, CF41, after treatment with melatonin and TGF-ß silencing. METHODS: Canine mammary cancer cell line, CF41, was cultured and characterized in relation to markers ER, PR and HER2. Cell line CF41 with reducing expression level of TGF-ßwas performed according to Leonel et al. (2017). Expression of the protein E-caderin, N-cadherin, vimentin and claudin-7 was evaluated by immunocytochemistry and quantified by optical densitometry. The analysis of cell migration was performed in transwell chambers with 8µM pore size membrane. RESULTS: CF41 cells present a triple negative phenotype, which is an aggressive phenotype. Immunocytochemistry staining showed increased expression of E-caderin and claudin-7 (P˂0.05) and decreased expression of N-cadherin and vimentin (P˂0.05) in CF41 cells after treatment with 1mM melatonin and TGF-ß silencing. Moreover, treatment with melatonin and TGF-ß silencing was able to reduce migration in cell line CF41 (P˂0.05). CONCLUSION: Our data suggests that therapies combining TGF- ß1 silencing and melatonin may be effective in suppressing the process of EMT, corroborating the hypothesis that melatonin acts on the TGF-ß1 pathway and can reduce the metastatic potential of CF41 cells. This is so far the first study that reports melatonin treatment in CF41 cells with TGF-ß1 silencing and its effect on EMT. Thus, further studies are needed to confirm this hypothesis.

Timing the impact of literacy on visual processing.

Learning to read requires the acquisition of an efficient visual procedure for quickly recognizing fine print. Thus, reading practice could induce a perceptual learning effect in early vision. Using functional magnetic resonance imaging (fMRI) in literate and illiterate adults, we previously demonstrated an impact of reading acquisition on both high- and low-level occipitotemporal visual areas, but could not resolve the time course of these effects. To clarify whether literacy affects early vs. late stages of visual processing, we measured event-related potentials to various categories of visual stimuli in healthy adults with variable levels of literacy, including completely illiterate subjects, early-schooled literate subjects, and subjects who learned to read in adulthood (ex-illiterates). The stimuli included written letter strings forming pseudowords, on which literacy is expected to have a major impact, as well as faces, houses, tools, checkerboards, and false fonts. To evaluate the precision with which these stimuli were encoded, we studied repetition effects by presenting the stimuli in pairs composed of repeated, mirrored, or unrelated pictures from the same category. The results indicate that reading ability is correlated with a broad enhancement of early visual processing, including increased repetition suppression, suggesting better exemplar discrimination, and increased mirror discrimination, as early as ∼ 100-150 ms in the left occipitotemporal region. These effects were found with letter strings and false fonts, but also were partially generalized to other visual categories. Thus, learning to read affects the magnitude, precision, and invariance of early visual processing.

Accuracy of two different criteria for neurophysiological intraoperative monitoring (NIOM) in spine/spinal cord surgeries / Acurácia de dois distintos critérios para monitorização neurofisiológica intraoperatória (MNIO) para cirurgias na coluna/medula

Our objective was to compeer the accuracy between two warning criteria during the intraoperative neurophysiologic monitorization for spine/spinal cord surgery. Method: We used two different warning criteria to detect neurological damage. The first criterion was the amplitude reduction of the somatossensory-evoked potentials (SEP) or motor-evoked potentials (MEP) greater than 50% at least in one limb and the second criterion was the complete loss of one of the same potentials. These results were compared with the neurological examination and the sensitivity, specificity, positive likelihood ratio (PLR) and negative likelihood ratio (NLR) was calculated for each criterion. Results: The sensitivity, specificity, PLR and NLR were respectively for criterion 1 and 2 (0,92/0,58; 0,96/0,99; 24/46 and 0,09/0,57). Conclusion: The first criterion suggests a better sensitivity and accuracy as a warning criterion to avoid central neurological damage...

Nosso objetivo foi comparar a acurácia entre dois critérios de alarme durante a monitorização neurofisiológica intraoperatória, em cirurgias de coluna ou medula. Método: Foram analisados dois critérios de alarme distintos para detectar danos neurológicos medulares, sendo o primeiro critério a redução maior que 50% na amplitude do potencial evocado somatossensitivo ou potencial evocado motor em pelo menos um membro. O segundo critério é a perda completa de um dos potenciais. Os achados foram comparados com as alterações neurológicas e a sensibilidade, especificidade, razão de verossimilhança positiva e negativa foram calculados para cada critério. Resultados: A sensibilidade, especificidade, razão de verossimilhança positiva e negativa foram, respectivamente, para os critérios 1 e 2 (0,92/0,58; 0,96/0,99; 24/46 e 0,09/0,57). Conclusão: O critério 1 aponta para uma tendência de melhor sensibilidade e acurácia, como sinal de alerta de um possível dano neurológico central...

Clinical features and neurologic progression of hyperargininemia.

Hyperargininemia is an autosomal recessive metabolic disorder caused by a deficiency of enzyme arginase I. It is a rare pan-ethnic disease with a clinical presentation distinct from that of other urea cycle disorders, and hyperammonemic encephalopathy is not usually observed. Hyperargininemia is one of the few treatable causes of pediatric spastic paraparesis, and can be confused with cerebral palsy. We retrospectively evaluated the clinical onset, neurologic manifestations, progression of abnormalities, electroencephalographic abnormalities, and laboratory findings of 16 Brazilian patients with hyperargininemia. Relevant data about the clinical spectrum and natural history of hyperargininemia are detailed. Progressive spastic diplegia constituted the key clinical abnormality in this group, but variability in clinical presentation and progression were evident in our series. Seizures in hyperargininemia may be more common than reported in previous studies. Features distinguishing hyperargininemia from cerebral palsy and hereditary spastic paraplegia are emphasized in this large series of patients.