Impact of glycerol feeding profiles on STEAP1 biosynthesis by Komagataella pastoris using a methanol-inducible promoter.

Currently, the lack of reliable strategies for the diagnosis and treatment of cancer makes the identification and characterization of new therapeutic targets a pressing matter. Several studies have proposed the Six Transmembrane Epithelial Antigen of the Prostate 1 (STEAP1) as a promising therapeutic target for prostate cancer. Although structural and functional studies may provide deeper insights on the role of STEAP1 in cancer, such techniques require high amounts of purified protein through biotechnological processes. Based on the results presented, this work proposes the application, for the first time, of a fed-batch profile to improve STEAP1 biosynthesis in mini-bioreactor Komagataella pastoris X-33 Mut+ methanol-induced cultures, by evaluating three glycerol feeding profiles-constant, exponential, and gradient-during the pre-induction phase. Interestingly, different glycerol feeding profiles produced differently processed STEAP1. This platform was optimized using a combination of chemical chaperones for ensuring the structural stabilization and appropriate processing of the target protein. The supplementation of culture medium with 6 % (v/v) DMSO and 1 M proline onto a gradient glycerol/constant methanol feeding promoted increased biosynthesis levels of STEAP1 and minimized aggregation events. Deglycosylation assays with peptide N-glycosidase F showed that glycerol constant feed is associated with an N-glycosylated pattern of STEAP1. The biological activity of recombinant STEAP1 was also validated, once the protein enhanced the proliferation of LNCaP and PC3 cancer cells, in comparison with non-tumoral cell cultures. This methodology could be a crucial starting point for large-scale production of active and stable conformation of recombinant human STEAP1. Thus, it could open up new strategies to unveil the structural rearrangement of STEAP1 and to better understand the biological role of the protein in cancer onset and progression.

Using lizards to evaluate the influence of average abundance on the variance of endoparasites in semiarid areas: dispersion and assemblage structure.

The distribution of parasites within host populations and communities, and the mechanisms responsible for these patterns, are poorly understood aspects of wildlife parasitology. Here, we evaluate the influence of the average abundance of endoparasite variance, using endoparasites of lizards from the Caatinga domain (semiarid region), north-eastern Brazil. We hypothesized that, due to the high number of generalist endoparasite species, they may occur randomly throughout host populations in an aggregate pattern. In addition, we evaluated the degree to which sample variance is influenced by the average abundance of endoparasite species, patterns of co-occurrence and dominance among endoparasite species and similarities between abundance and the richness of endoparasite infracommunities in several host species. Between September 2015 and February 2016, 2141 lizards (1233 infected) from 16 species were collected from six Caatinga areas. In total, 25,687 endoparasites were collected, which belonged to 13 species including nematodes, pentastomids, cestodes, trematodes and acanthocephalans. Parasite-host associations documented here included 39 newly identified interactions. Endoparasites occurred in a typical aggregate pattern of distribution within their hosts; there was no measurable preference related to the acquisition of hosts by endoparasites. Despite the new records, endoparasites found were commonly associated with lizards in Caatinga environments, which may reflect fauna composed of generalist endoparasite species.

Dual role of histamine on microglia-induced neurodegeneration.

Several hypotheses have been raised about the dual role of histamine in neurological disorders, and evidences have shown its crucial involvement in the modulation of microglia-mediated neuroinflammation. Previously, we reported that the administration of histamine induces a deleterious effect by promoting a pro-inflammatory phenotype on microglia that in turn compromises dopaminergic neuronal survival. Contrary, under lipopolysaccharide challenge, histamine inhibits the injurious effect of microglia-mediated inflammation, protecting dopaminergic neurons, suggesting that the modulation of microglial activity is dependent on the environmental context. Thus, histamine and/or histamine receptor agonists may serve to develop new therapeutic approaches to overcome neurodegenerative disorders.

Urinary metabolomic profiling of asthmatics can be related to clinical characteristics.

Metabolomics has been increasingly explored to achieve an improved understanding of asthma. In the current observational and exploratory study, the first to have examined the relationship between oxidative stress extension, eosinophilic inflammation, and disease severity in asthmatic patients, metabolomics (using target aliphatic aldehydes and alkanes) was carried out using solid-phase microextraction (SPME) followed by a comprehensive two-dimensional gas chromatography coupled to mass spectrometry with a high-resolution time-of-flight analyzer (GC×GC-ToFMS). We were able to demonstrate that metabolomics can give valuable insights into asthma mechanisms once lipidic peroxidation assessed by urinary metabolomics is related to the clinical characteristics of nonobese asthmatics, such as disease severity, lung function, and eosinophilic inflammation. Nevertheless, considering our sample size, the obtained results require further validation using a much larger sample cohort.

Encapsulation of essential oils in SiO2 microcapsules and release behaviour of volatile compounds.

Natural substances derived from plants such as essential oils (EOs) are used in a variety of applications such as in the release of fragrances or active substances in cosmetics, in food industries to protect sensitive ingredients against oxidative processes and as antimicrobial agents. However, the labile and volatile nature of EOs reduces their activity during application or storage. Here, the microencapsulation of EOs in silica capsules was investigated as a mean to control the fast release of their volatile constituents. The preparation of silica capsules with oil cores was obtained by employing a sol-gel method to oil-in-water-in-oil (O/W/O) multiple emulsions. The volatile release from the SiO2 capsules was investigated by comprehensive two-dimensional gas chromatography with time of flight mass spectrometry detection (GC × GC-ToFMS). This research demonstrates that the SiO2 capsules have selectively encapsulated the different volatile species and the corresponding release profiles depend on the chemical properties of each component.

Glycolysis Inhibition as a Strategy for Hepatocellular Carcinoma Treatment?

Hepatocellular carcinoma (HCC) is the most frequently detected primary malignant liver tumor, representing a worldwide public health problem due to its high morbidity and mortality rates. The HCC is commonly detected in advanced stage, precluding the use of treatments with curative intent. For this reason, it is crucial to find effective therapies for HCC. Cancer cells have a high dependence of glycolysis for ATP production, especially under hypoxic environment. Such dependence provides a reliable possible strategy to specifically target cancer cells based on the inhibition of glycolysis. HCC, such as other cancer types, presents a clinically well-known upregulation of several glycolytic key enzymes and proteins, including glucose transporters particularly glucose transporter 1 (GLUT1). Such enzymes and proteins constitute potential targets for therapy. Indeed, for some of these targets, several inhibitors were already reported, such as 2-Deoxyglucose, Imatinib or Flavonoids. Although the inhibition of glycolysis presents a great potential for an anticancer therapy, the development of glycolytic inhibitors as a new class of anticancer agents needs to be more explored. Herein, we propose to summarize, discuss and present an overview on the different approaches to inhibit the glycolytic metabolism in cancer cells, which may be very effective in the treatment of HCC.

Targeting STEAP1 Protein in Human Cancer: Current Trends and Future Challenges.

Cancer is a global health issue that impairs the life quality of patients and origins thousands of deaths annually worldwide. Six-transmembrane epithelial antigen of the prostate (STEAP1) was identified to be overexpressed in several types of cancers, namely in prostate cancer (PCa). Considering its secondary structure, associated with its location in the cell membrane, has been suggested a role in intercellular communication between tumour cells. Taking into account its high specificity and overexpression in human cancers, STEAP1 is nowadays a promising candidate to be imposed as a therapeutic target. Several strategies have been developed during the last few years for targeting STEAP1, including antibody-drug conjugates, monoclonal antibodies (mAbs), DNA vaccines and small noncoding RNAs (ncRNAs). This review presents the current knowledge about STEAP1 protein expression in human tissues, its biochemical properties and targeting strategies with the purpose to evaluate its potential as therapeutic agent for cancer.

Epidemiological Profile of Wild Rabies in Brazil (2002-2012).

Rabies is one of the most important zoonosis in the world with high impact on public health. Studies report the presence of Lyssavirus in reservoirs of the wild cycle, highlighting the role of wild canines, marmosets, and vampire and non-vampire bats as potential vectors of the disease to domestic animals and human beings. Therefore, the reintroduction of rabies in urban environments from reservoirs of the wild cycle is a matter of concern. This study describes the profile of rabies cases documented in Brazil from 2002 to 2012, with emphasis on the wild transmission cycle of the disease. We carried out a descriptive study using records with information on the time of infection, persons with infection and location of confirmed cases of rabies in humans and animals, as well as data on anti-rabies treatments obtained from the Information System of Notifiable Diseases (Sinan) database. Within the study period, 82 cases of rabies transmitted by wild animals to humans were reported, predominantly in rural areas of the northern and north-eastern regions. Of the cases in humans, 72% did not receive post-exposure prophylaxis. Among wild mammals, vampire bats were the most frequent vectors of the disease. In the north-east region, 460 terrestrial wild mammals were reported with confirmed rabies. Over the study period, 1703 bats were reported to carry the rabies virus. In the south-east region, the most frequently reported carriers of the virus were non-vampire bats. The midwest and northern regions presented a lower number of records of rabies cases among terrestrial wild mammals. However, the high number of rabies cases among bovines reflects the role of the vampire bat as a maintainer of the rabies virus in the rural cycle. The present results are key to adjust the planning of rabies control in Brazil to the current epidemiological trends.

Leptin levels, beta-cell function, and insulin sensitivity in families with congenital and acquired generalized lipoatropic diabetes.

Lipoatropic diabetes (LD) designates a group of syndromes characterized by diabetes mellitus with marked insulin resistance and either a localized or generalized absence of adipose tissue. In this study, we evaluated plasma leptin levels in subjects with congenital generalized lipoatropic diabetes (CGLD, n = 11) or acquired generalized lipoatropic diabetes (AGLD, n = 11), and assessed correlations between leptin levels and estimations of insulin secretion and insulin sensitivity using homeostasis model assessment (HOMA). Leptin levels were 0.86 +/- 0.32, 1.76 +/- 0.78, and 6.9 +/- 4.4 ng/mL in subjects with CGLD, AGLD, and controls (n = 19), respectively (ANOVA P < 0.0001). Specific insulin levels were 154 +/- 172, 177 +/- 137 and 43 +/- 22 pmol/L, respectively (P < 0.0001). Insulin sensitivity was significantly decreased in both groups with LD (P < 0.0001), whereas HOMA beta-cell function was not significantly different when compared with controls. Leptin levels were significantly correlated with body mass index, insulin levels, and HOMA beta-cell function, and inversely correlated with insulin sensitivity in control subjects but not in subjects with generalized LD. In conclusion, decreased leptin levels were observed in subjects with generalized LD, with a trend towards lower levels in the acquired than in the congenital form (P = 0.06). The temporal relationship between the decrease in leptin levels and the development of lipoatrophy should be investigated in at-risk young relatives of subjects with the acquired forms to assess the usefulness of leptin levels as a marker of lipoatrophy.

Demonstration of pectic polysaccharides in cork cell wall from Quercus suber L.

Scanning electron microscopy (SEM) and chemical analysis were used to observe the cell wall changes that occur in cork with "mancha amarela", when compared to a standard cork. To mimic the microbial attack exhibited in cork with mancha amarela, the standard cork was treated enzymatically with commercial pectinase and hemicellulase preparations. The tissues treated with pectinase were comparable with those attacked with mancha amarela. Both were composed by deformed and wrinkly cells and exhibited cell wall separation at the middle lamella level, which suggests solubilization/removal of the pectic polysaccharides. The cork cell wall material, prepared as alcohol-insoluble residue, was fractionated by hot water (Pect(H)()2(O)) and hot dilute acid (Pect(acid)). The relatively large amount of hexuronic acid and the occurrence of Ara in the SPect(H)()2(O) and SPect(acid) allow to confirm, as far as we know, for the first time the presence of pectic polysaccharides in the cell walls of cork from Quercus suber L. They accounted for ca. 1.5% of the cork and may consist of polymers with long side chains of arabinosyl residues. These polymers have to be taken into account in any realistic model of the cork cell wall. Cork with mancha amarela contained a smaller amount of pectic polysaccharides (ca. 0.5%), which confirms that the cellular separation observed by SEM is related to the degradation/removal of the middle lamella pectic polysaccharides.

Detection of rancid defect in virgin olive oil by the electronic nose.

A sensor array of 32 conducting polymer sensors has been used to detect the rancid defect in virgin olive oils. A training set, composed of admixtures of a Portuguese virgin olive oil with different percentages (0-100%) of a rancid standard oil, was used for the selection of the best sensors classifying correctly the samples. Information on volatile compounds responsible for rancidity and the sensory evaluation of samples by assessors were used for explaining the mathematical selection of sensors. A tentative calibration, using unsupervised procedures (PCA and MDS) and a nonlinear regression, was carried out, with the training set, and later confirmed with a test set with which rancid commercial samples of different varieties were used to spike a Greek extra virgin olive oil at low levels of rancidity (0.5-6%).

Enzymatic isolation and structural characterisation of polymeric suberin of cork from Quercus suber L.

An enzymatic method has been used to isolate, for the first time, polymeric suberin from the bark of Quercus suber L. or cork. This was achieved by solvent extraction (dichloromethane, ethanol and water), followed by a step-by-step enzymatic treatment with cellulase, hemicellulase and pectinase, and a final extraction with dioxane/water. The progress of suberin isolation was monitored by Fourier transform infrared spectroscopy using a photoacoustic cell (FTIR-PAS). The material obtained (polymeric suberin (PS)) was characterised by solid-state and liquid-state nuclear magnetic resonance, FTIR-PAS and vapour pressure osmometry, and compared with the suberin fraction obtained by alkaline depolymerisation (depolymerised suberin (DS)). The results showed that PS is an aliphatic polyester of saturated and unsaturated fatty acids, with an average molecular weight (M(w)) of 2050 g mol(-1). Although this fraction represents only 10% of the whole suberin of cork, its polymeric nature gives valuable information about the native form of the polymer. DS was found to have an average M(w) of 750 g mol(-1) and to comprise a significant amount of acidic and alcoholic short aliphatic chains.

Involvement and fragmentation: a study of parental care of hospitalized children in Brazil.

Parental involvement in the care of children who are hospitalized has been encouraged by the government in Brazil, as it has in the United Kingdom (UK). In this paper, key aspects of the UK, North American, and Latin American literature concerning parental participation are discussed, and implications for hospital care of children in Brazil are considered. A study of the division of work between nurses and the mothers (or other relatives) of 10 children hospitalized with chronic illnesses is reported. Data were collected by participant observation of child care in a Brazilian hospital. The results highlight some of the difficulties that arise in the integration of the work of mothers and nurses in hospital care of children and the fragmentation of care into "manual" and "intellectual" work. The results are considered within the theoretical framework of the model of technologic organization of work (Gonçalves, 1979, 1994). Implications for the organization of child care in the hospital are discussed.

[Nursing care in neonatal units: measures for the prevention of cross infections]. / Assistência de enfermagem em unidade de internação neonatal: medidas para prevenção de infecções hospitalares.

The prevention of infection in nurseries requires measures related to nursing care in terms of the environment, equipment, personnel and the newborn. In view of the problems related to hospital infection, the objective of the present investigation was to determine the relationship between prescriptive measures for the Prevention of Infection and activities effectively carried out In a Neonatal Admission Unit. Participant observation and semistructured interviews were the strategies used for the investigation which allowed data collection. With this research we could see that prophylactic measures need to be taken together in a collection of activities based on adequate structure and facilities, performed by a cohesive professional team where everybody work towards the same goal. Measures taken isolated do not contribute to the effective accomplishment of prescriptions.

[The process of nursing work in collective health and interdisciplinary studies]. / O processo de trabalho da enfermagem em saúde coletiva e a interdisciplinaridade.

This study aims at discussing and stimulating reflections on the need of an interdisciplinary dialogue when the object of work is the health-illness-care process. The authors discuss the definition of Nursing by considering its essence, care, its history and practice. Following, considerations about inter- and trans-disciplinary studies on collective health are presented and the authors conclude with a proposal of basing care on the theory of communicative action developed by Jürgen Habermas.

[Care of hospitalized children: reflexions about the participation of parents]. / Assistência à criança hospitalizada: reflexões acerca da participação dos pais.

The care of a child admitted in the hospital is going through meaningful changes and, in a more actual approach, the main strategy seems to stimulate parents or relatives to stay with their children in the hospital. The purpose of this study is to analyse parents' participation in the process of staying in the hospital with their children. We have chosen the qualitative method and used as a theoretic--methodological reference the Model of Technological Work Organization. Based on the process of work, we have pointed out that bringing mothers to the ward is not so simple as it interferes in the reorganization of the work at the theoretical and practical levels. Concepts such as co-operation and partnership are built, however, sharing knowledge, power and room is not a simple action. It implies in changes of values and postures by parents and professionals.

[Agents of nursing in São Paulo health practices: from the bacteriological model to the health program (1889-1983)]. / Os agentes de enfermagem nas práticas sanitárias paulistas: do modelo bacteriológico à programação em saúde (1889-1983).

The historical roots of the nursing profession in public health in the state of São Paulo from 1900-1980 have been identified. Nurses have effectively participated to implement a new public health program--"Programação em Saúde", having the assignment to train, coordinate, supervise/manage other nurses who lacked specialized training. The nurse's understanding of her role in the health process was limited to individual performance with emphasis on technical ability, without understanding the purpose of her actions in the overall model.

[Pediatric nursing knowledge: books edited in Brazil from 1916 to 1988]. / O conhecimento em enfermagem pediátrica: livros editados no Brasil de 1916 a 1988.

From the apprehension of the knowledge in pediatrics nursing in Brazil, a research was done in a Brazilian historical bibliographic work of references. From an historical perspective nursing it is seen as a social articulate practice, as part of a collective process of work. The knowledge in this study is considered as an instrument from which man apprehends his working object. Forty titles were found about how to take care of children, from eight per cent of the a group of five hundred and four. The proportion was considered very small. The production which was found was classified under two aspects: the prescriptive and the analytical. The prescriptive texts are those related to normalize the work in view of the rationality and to the productivity. The analytical opens the possibility and give the means to diversify the nursing assistance particularizing the care and with another aim related to the nursing work.

[Bibliographic study of the mother-child relationship: basis for pediatric and neonatal care]. / Um estudo bibliográfico sobre o apego mãe e filho: bases para a assistência de enfermagem pediátrica e neonatal.

The study consists of a bibliographical review about the mother and son attachment and its considerations in nursing care intervention, in the child's hospitalization process. In deciding to study this theme we had the purpose to obtain knowledge that would be useful in daily pediatric and neonatal nursing practice. We evidenced the importance of knowledge dissemination about the attachment among the nursing professionals, because their performance can interfere in a significant way in the hospitalized child's social and emotional development. However, in spite of the importance of the theme, few scientific studies in the nursing area were published. For our theoretical knowledge we searched another knowledge areas as psychology, sociology and anthropology.

[Organization of neonatal nursing in the region of Ribeirão Preto-SP. Brazil-1992]. / A organização do trabalho na assistência ao recém-nascido em berçários da regional de Ribeirão Preto-SP. Brasil-1992.

The present study analyses the organization of newborn care in different nurseries in the region of Ribeirão Preto as well as how nursing participates in this work. Through observation and interviews in 4 nurseries, we found that the work organization varies according to the hospital size and complexity. Action is centred on the child and in more complex cases, priority is given to the pathology and clinical care. We also observe enlarged actions, involving the binomial mother-child and the family. The quality of care is a result of a complex combination of human resources, material and installation. Bigger and more complex institutions present a diversity of personnel, more bureaucracy and hierarchy, information and technology system, routine procedures by written norms and more sophisticated equipment. The object of action is centred on the child, but there are practices in which the object is enlarged to the binomial mother-child and the family.