The metastatic process in breast cancer is related to the expression of the epithelial-to-mesenchymal transition transcription factors (EMT-TFs) SNAIL, SLUG, SIP1 and TWIST1. EMT-TFs and nuclear ...factor-κB (NF-κB) activation have been associated with aggressiveness and metastatic potential in carcinomas. Here, we sought to examine the role of NF-κB in the aggressive properties and regulation of EMT-TFs in human breast cancer cells. Blocking NF-κB/p65 activity by reducing its transcript and protein levels (through siRNA-strategy and dehydroxymethylepoxyquinomicin DHMEQ treatment) in the aggressive MDA-MB-231 and HCC-1954 cell lines resulted in decreased invasiveness and migration, a downregulation of SLUG, SIP1, TWIST1, MMP11 and N-cadherin transcripts and an upregulation of E-cadherin transcripts. No significant changes were observed in the less aggressive cell line MCF-7. Bioinformatics tools identified several NF-κB binding sites along the promoters of SNAIL, SLUG, SIP1 and TWIST1 genes. Through chromatin immunoprecipitation and luciferase reporter assays, the NF-κB/p65 binding on TWIST1, SLUG and SIP1 promoter regions was confirmed. Thus, we suggest that NF-κB directly regulates the transcription of EMT-TF genes in breast cancer. Our findings may contribute to a greater understanding of the metastatic process of this neoplasia and highlight NF-κB as a potential target for breast cancer treatment.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A granular sludge sequencing batch reactor (SBR) was operated for 340 days for treating a synthetic wastewater containing fluoroquinolones (FQs), namely ofloxacin, norfloxacin and ciprofloxacin. The ...SBR was intermittently fed with FQs, at concentrations of 9 and 32 μM. No evidence of FQ biodegradation was observed but the pharmaceutical compounds adsorbed to the aerobic granular sludge, being gradually released into the medium in successive cycles after stopping the FQ feeding.
Overall COD removal was not affected during the shock loadings. Activity of ammonia oxidizing bacteria and nitrite oxidizing bacteria did not seem to be inhibited by the presence of FQs (maximum of 0.03 and 0.01 mM for ammonium and nitrite in the effluent, respectively). However, during the FQs feeding, nitrate accumulation up to 1.7 mM was observed at the effluent suggesting that denitrification was inhibited. The activity of phosphate accumulating organisms was affected, as indicated by the decrease of P removal capacity during the aerobic phase. Exposure to the FQs also promoted disintegration of the granules leading to an increase of the effluent solid content, nevertheless the solid content at the bioreactor effluent returned to normal levels within ca. 1 month after removing the FQs in the feed allowing recovery of the bedvolume. Denaturing gradient gel electrophoresis revealed a dynamic bacterial community with gradual changes due to FQs exposure. Bacterial isolates retrieved from the granules predominantly belonged to α- and γ-branch of the Proteobacteria phylum.
The capacity of the system to return to its initial conditions after withdrawal of the FQ compounds in the inlet stream, reinforced its robustness to deal with wastewaters containing organic pollutants.
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•Effect of ofloxacin, norfloxacin and ciprofloxacin on aerobic granules was studied.•Fluoroquinolones adsorbed reversibly onto granular sludge, no biodegradation occurred.•Prolonged fluoroquinolones feeding led to nitrate accumulation in the SBR effluent.•Exposure to fluoroquinolones destabilized the granules.•Granules quickly recovered after withdrawing fluoroquinolones from influent.
Over the last years, heavy ethanol consumption by teenagers/younger adults has increased considerably among females. However, few studies have addressed the long-term impact on brain structures' ...morphology and function of chronic exposure to high ethanol doses from adolescence to adulthood in females. In line with this idea, in the current study we investigated whether heavy chronic ethanol exposure during adolescence to adulthood may induce motor impairments and morphological and cellular alterations in the cerebellum of female rats. Adolescent female Wistar rats (35 days old) were treated with distilled water or ethanol (6.5 g/kg/day, 22.5% w/v) during 55 days by gavage. At 90 days of age, motor function of animals was assessed using open field (OF), pole, beam walking and rotarod tests. Following completion of behavioral tests, morphological and immunohistochemical analyses of the cerebellum were performed. Chronic ethanol exposure impaired significantly motor performance of female rats, inducing spontaneous locomotor activity deficits, bradykinesia, incoordination and motor learning disruption. Moreover, histological analysis revealed that ethanol exposure induced atrophy and neuronal loss in the cerebellum. These findings indicate that heavy ethanol exposure during adolescence is associated with long-lasting cerebellar degeneration and motor impairments in female rats.
Puberty is a complex biological event that requires maturation of the reproductive neuroendocrine axis and subsequent initiation of high-frequency, episodic release of GnRH and LH. Nutrition is a ...critical factor affecting the neuroendocrine control of puberty. Although nutrient restriction during juvenile development delays puberty, elevated rates of body weight gain during this period facilitate pubertal maturation by programming hypothalamic centers that underlie the pubertal process. Recent findings suggest that maternal nutrition during gestation can also modulate the development of the fetal neuroendocrine axis, thus influencing puberty and subsequent reproductive function. Among the several metabolic signals, leptin plays a critical role in conveying metabolic information to the brain and, consequently, controlling puberty. The effects of leptin on GnRH secretion are mediated via an upstream neuronal network because GnRH neurons do not express the leptin receptor. Two neuronal populations located in the arcuate nucleus that express the orexigenic peptide neuropeptide Y (NPY), and the anorexigenic peptide alpha melanocyte-stimulating hormone (αMSH), are key components of the neurocircuitry that conveys inhibitory (NPY) and excitatory (αMSH) inputs to GnRH neurons. In addition, neurons in the arcuate nucleus that coexpress kisspeptin, neurokinin B, and dynorphin (termed KNDy neurons) are also involved in the metabolic control of puberty. Our studies in the bovine female demonstrate that increased planes of nutrition during juvenile development lead to organizational and functional changes in hypothalamic pathways comprising NPY, proopiomelanocortin (POMC, the precursor of αMSH), and kisspeptin neurons. Changes include alterations in the abundance of NPY, POMC, and Kiss1 mRNA and in plasticity of the neuronal projections to GnRH neurons. Our studies also indicate that epigenetic mechanisms, such as modifications in the DNA methylation pattern, are involved in this process. Finally, our most recent data demonstrate that maternal nutrition during gestation can also induce morphological and functional changes in the hypothalamic NPY system in the heifer offspring that are likely to persist long after birth. These organizational changes occurring during fetal development have the potential to not only impact puberty but also influence reproductive performance throughout adulthood in the bovine female.
•Nutrition is a critical factor controlling pubertal maturation in heifers.•Leptin conveys metabolic information to the brain and controls puberty.•Leptin's effects are mediated via upstream neurons including neuropeptide Y and proopiomelanocortin neurons.•Nutrition during early life leads to functional changes in hypothalamic pathways.•Gestational nutrition impacts brain development and puberty in the heifer offspring.
Synthetic biphasic calcium phosphate (BCP) granules and powder are biocompatible biomaterials with a well-known capacity for osteoconduction, presenting very satisfactory clinical and histological ...results. It remains unanswered if the putty configuration impacts the biological response to the material. In this study, we aimed to compare the cytocompatibility and biocompatibility of nanostructured BCP in the putty configuration (moldable nanostructured calcium phosphate, MnCaP) on the healing of critical-sized bone defects (8 mm) in rat calvaria. Cytocompatibility was determined through the viability of fibroblast cells (V-79) to the extracts of different concentrations of MnCaP. Forty-five Wistar rats were randomly divided into three groups (
= 15)-clot, MnCaP, and commercial biphasic calcium phosphate in granules configurations (Nanosynt
)-and subdivided into three experimental periods (1, 3, and 6 months). Histological, histomorphometric, and microtomographic analyses allowed the evaluation of newly formed bone, residual biomaterial, and connective tissue. The in vitro evaluation showed that MnCaP was cytocompatible. The histomorphometric results showed that the Nanosynt
group granted the highest new-formed bone values at six months (
< 0.05), although the biomaterial volume did not differ between groups. The putty configuration was easier to handle, and both configurations were biocompatible and osteoconductive, presented similar biosorption rates, and preserved the calvaria architecture.
Abstract Purposes To analyze which Beck Depression Inventory-II (BDI-II) and Postpartum Depression Screening Scores (PDSS) total and dimensional scores, as well as symptomatic answers proportions ...significantly differ between women in the perinatal period (pregnant/postpartum) without major depression, with major depression and women outside the perinatal period. Methods 572 pregnant women in the third trimester completed Beck Depression Inventory-II and Postpartum Depression Screening Scale and were assessed with the Diagnostic Interview for Genetic Studies. 417 of these were also assessed (with the same instruments) at three months postpartum. Ninety non-pregnant women or that did not have a child in the last year (mean age=29.42±7.159 years) also filled in the questionnaires. Results Non-depressed pregnant women showed lower scores than depressed pregnant women and higher scores than women outside the perinatal period in the BDI-II total score and in its Somatic-Anxiety dimension. Non-depressed postpartum women showed significantly higher scores than women outside the perinatal period only at Sleep/Eating Disturbances. Compared to women outside the perinatal period, pregnant women without depression presented higher scores only in the somatic items. Women with vs. without depression in the postpartum period did not significantly differ and both presented higher scores than women outside the perinatal period in the proportions of loss of energy and sleep changes. Limitations Women outside the perinatal period were not diagnosed for the presence of a depressive disorder, but their BDI-II mean score was similar to the figures reported worldwide regarding women in childbearing age. Conclusion In the perinatal period, most particularly at pregnancy, women experience significant somatic changes even if not clinically depressed. Cognitive-affective symptoms are more useful when assessing the presence of perinatal depression.
Abstract The American Barn Owl (Tyto furcata) lives in urban, periurban and wild environments and feeds mainly on small rodents, meaning it has great importance in the biological control of pests. ...The aim of this work was to describe the reproductive, parental and eating habits of a pair of American barn owls naturally living outside a residence in the urban area of the municipality of Campos dos Goytacazes, Rio de Janeiro state, Brazil. A wood box was installed on an outside wall of the home, monitored by a video camera. A spreadsheet was created to keep track of the observations recorded. The female laid four eggs, and after an incubation period of 30-32 days all the eggs hatched, but only two chicks survived after cannibalism among the chicks. Initially, the male provided the food to the chicks and the female remained in the nest caring for the brood. After approximately a month, the female also began to leave the nest and return with prey, which was offered to the chicks, with the male also continuing this behavior. The chicks left the nest in September, 2017. The data obtained show the existence of cooperation and division of tasks between male and female owls during the reproductive period.
Resumo A coruja-das-torres americana (Tyto furcata) vive em ambientes urbanos e se alimenta principalmente de pequenos roedores, sendo de grande importância no controle biológico de pragas. O objetivo deste trabalho foi descrever os hábitos alimentares, parentais e reprodutivos de um casal de corujas-das-torres americanas, naturalmente vivendo fora de uma residência na zona urbana do município de Campos dos Goytacazes, estado do Rio de Janeiro, Brasil. Uma caixa de madeira foi instalada em uma parede externa da casa, monitorada por uma câmera de vídeo. Uma planilha foi criada para manter o controle das observações registradas. A fêmea pôs quatro ovos, e após período de incubação de 30-32 dias todos os ovos eclodiram, mas apenas dois filhotes sobreviveram após o canibalismo entre os filhotes. Inicialmente, o macho fornecia a comida aos filhotes e a fêmea permanecia no ninho cuidando da ninhada. Depois de cerca de um mês, a fêmea também começou a sair do ninho e voltar com a presa, que era oferecida aos filhotes, com o macho também continuando com esse comportamento. Os filhotes deixaram o ninho em setembro de 2017. Os dados obtidos mostram a existência de cooperação e divisão de tarefas entre corujas machos e fêmeas durante o período reprodutivo.
This article describes a new concept to reduce carbon dioxide emissions of offshore oil production of high gas-to-oil ratio reservoirs and high content of CO2, denominated Offshore Salt Cavern ...Ultra-deep Water CCS (Carbon Capture and Storage) System. This hybrid system is intended for natural gas storage, the gravitational separation between CO2/CH4, and CO2 confinement for final destination. This development emerged from a current demand of some Brazilian pre-salt reservoirs to destinate a gas stream with high CO2 contamination, produced during the oil extraction. These reservoirs have a continuous salt rock layer of 2000 m as caprock making the construction possible of salt caverns by leaching using seawater. In the first stage of technology development, the system will only store a gas stream contaminated with a high concentration of CO2. In the second stage of its development, it will allow not only the separation of natural gas from the CO2 but also its storage and the monetization of CH4. This paper presents the conceptual design of this technology, showing the steps from the parametric study to select the best relation between flowrate, leaching time, structural stability, and the volume of gas with the high content of CO2 storage, up to the final geomechanical design using the set of parameters selected.
The digital ratio between the second and fourth digits of the hands, known as 2D:4D, is sexually dimorphic. It has been suggested that a low 2D:4D indicates high exposure to prenatal testosterone and ...low estrogen exposure while a high 2D:4D indicates the inverse. The 2D:4D may be predictive of cancer susceptibility, and this may be particularly true in cancers that show differences between sexes in their occurrence.
To conduct a systematic review of published epidemiological literature examining the association between 2D:4D and cancer.
This review was carried out according to criteria recommended for the systematic review of Statement PRISMA. We enrolled 25 papers involving eleven cancer topographies with 4,569 cases and 19,416 controls from Europe, America, Asia and Australia.
We noticed variations and discrepancies in the results of the association between 2D:4D and cancer among the studies, either in those that had evaluated the same or different types of cancer, or in the same or distinct lateralities. However, a high 2D:4D was considered a likely predictor of cancer risk in 11 of 25 studies, a low 2D:4D was suggested as a predictor of risk in eight papers, and five of the twenty-five studies did not demonstrate any association.
Although this biomarker has the advantage of being easy to measure, it is noted that its relationship with sex hormone levels at specific stages of life has not yet been well quantified, and it has still been questioned. Hence, it is suggested that those findings from studies involving 2D:4D as a proxy for foetal hormone exposure should be interpreted with caution, as well as those studies which claim its association with cancer. Thus, this review shows the need for a greater number of epidemiological studies using more homogeneous methodology and techniques to better investigate the strength of the findings.
•The ratio of the lengths of the index and ring fingers, 2D:4D, is often employed as marker of prenatal sex hormone exposure.•The 2D:4D may be considered a predictive biomarker for cancer risk, mainly in prostate, breast and gastric cancers.•The association between 2D:4D and cancer was evaluated in 25 papers involving eleven distinct topographies.•The 2D:4D has been claimed to be negatively correlated to prenatal testosterone exposure and positively to oestrogen.
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