Characterization of subventricular zone-derived progenitor cells from mild and late symptomatic YAC128 mouse model of Huntington's disease

Huntington's disease (HD) is caused by an expansion of CAG repeats in the HTT gene, leading to expression of mutant huntingtin (mHTT) and selective striatal neuronal loss, frequently associated with mitochondrial dysfunction and decreased support of brain-derived neurotrophic factor (BDNF). New neurons derived from the subventricular zone (SVZ) are apparently not able to rescue HD pathological features. Thus, we analyzed proliferation, migration and differentiation of adult SVZ-derived neural stem/progenitor cells (NSPC) from mild (6 month-old (mo)) and late (10 mo) symptomatic HD YAC128 mice expressing full-length (FL)-mHTT versus age-matched wild-type (WT) mice. SVZ cells derived from 6 mo YAC128 mice exhibited higher migratory capacity and a higher number of MAP2 + and synaptophysin + cells, compared to WT cells; MAP2 labeling was enhanced after exposure to BDNF. However, BDNF-evoked neuronal differentiation was not observed in 10 mo YAC128 SVZ-derived cells. Interestingly, 6 mo YAC128 SVZ-derived cells showed increased intracellular Ca²⁺ levels in response to KCl, which was potentiated by BDNF, evidencing the presence of differentiated neurons. In contrast, KCl depolarization-induced intracellular Ca²⁺ increase in 10 mo YAC128 SVZ-derived cells was shown to be increased only in BDNF-treated YAC128 SVZ-derived cells, suggestive of decreased differentiation capacity. In addition, BDNF-untreated NSPC from 10 mo YAC128 mice exhibited lower mitochondrial membrane potential and increased mitochondrial Ca²⁺ accumulation, in relation with NSPC from 6 mo YAC128 mice. Data evidence age-dependent reduced migration and decreased acquisition of a neuronal phenotype, accompanied by decreased mitochondrial membrane potential in SVZ-derived cells from YAC128 mice through HD symptomatic phases.     

Susceptibility of <Emphasis Type="Italic">Candida albicans</Emphasis> from Cystic Fibrosis Patients

Candida albicans is a common microbe, colonizer and potential pathogen found in respiratory cultures of cystic fibrosis (CF) patients. Because of possible development of resistance in patient isolates resulting from residence in the abnormal milieu of CF patient airways, or from exposure to antifungals, and considering the possibility of patient-to-patient spread of microbes and reports of elevated resistance to other fungal pathogens, it was important to assay the susceptibility of isolates of Candida and compare that profile to isolates from the community. In our center, and unlike another fungal pathogen, no increase in resistance of Candida isolates of the CF cohort was found.     

Physiological responses and biofilter potential of <Emphasis Type="Italic">Hypnea aspera</Emphasis> (Rhodophyta,Gigartinales) cultivated in different availabilities of nitrate,ammonium, and phosphate

Along with the search for new species of seaweeds with biofilter capacity, it is also necessary to understand the physiological and biochemical responses of these seaweeds cultivated in different availabilities of nitrate, ammonium, and phosphate. To accomplish this, a laboratory study was performed to evaluate the ability of Hypnea aspera Kützing (Gigartinales, Rhodophyta), to growth under different nitrate, ammonium, and phosphate availabilities and to uptake, assimilate, and remove these nutrients from seawater. Treatments were composed of sterilized seawater enriched with quarter-strength von Stosch’s nutrient solution modified (without any nitrogen and phosphorus compounds). Nitrate or ammonium, together with phosphate, was added in combined N/P ratios of 100:1 and 10:1. Nitrate concentrations varied from 0 to 150 μM, and ammonium concentrations varied from 0 to 70 μM. Growth rates of H. aspera increased with nitrate addition, and the highest value was 4.68 ± 0.76 % day^?1 in 150 μM, but the addition of high ammonium concentration (70 μM) in N/P ratio of 10:1 inhibited the growth rates (?3.89 ± 1.03 % day^?1). Nitrogen was accumulated as proteins and phycobiliproteins, mainly phycoerythrin, at higher phosphate availability (N/P ratio of 10:1) for nitrate addition (150 μM for proteins and 50, 100, and 150 μM for phycoerythrin), and lower phosphate availability (N/P ratio of 100:1) for ammonium addition (50 and 70 μM for proteins and 50 μM for phycoerythrin). Nitrogen and phosphate were assimilated into thallus in all treatments with nutrient addition. Hypnea aspera showed high removal efficiency (higher than 90 %) of nitrate, nitrite, ammonium, and phosphate present in the seawater. These results suggest that H. aspera could be cultivated in integrated multitrophic aquaculture systems to reduce nutrient loading in eutrophic seawater.     

Ibuprofen reverts antifungal resistance on Candida albicans showing overexpression of CDR genes

Several mechanisms may be associated with Candida albicans resistance to azoles. Ibuprofen was described as being able to revert resistance related to efflux activity in Candida . The aim of this study was to uncover the molecular base of antifungal resistance in C. albicans clinical strains that could be reverted by ibuprofen. Sixty-two clinical isolates and five control strains of C. albicans were studied: the azole susceptibility phenotype was determined according to the Clinical Laboratory for Standards Institute, M27-A2 protocol and minimal inhibitory concentration values were recalculated with ibuprofen (100 μg mL⁻¹); synergistic studies between fluconazole and FK506, a Cdr1p inhibitor, were performed using an agar disk diffusion assay and were compared with ibuprofen results. Gene expression was quantified by real-time PCR, with and without ibuprofen, regarding CDR1 , CDR2 , MDR1 , encoding for efflux pumps, and ERG11 , encoding for azole target protein. A correlation between susceptibility phenotype and resistance gene expression profiles was determined. Ibuprofen and FK506 showed a clear synergistic effect when combined with fluconazole. Resistant isolates reverting to susceptible after incubation with ibuprofen showed CDR1 and CDR2 overexpression especially of the latter. Conversely, strains that did not revert displayed a remarkable increase in ERG11 expression along with CDR genes. Ibuprofen did not alter resistance gene expression significantly ( P >0.05), probably acting as a Cdrp blocker.     

Quantification of polymeric mannose in wine extracts by FT-IR spectroscopy and OSC-PLS1 regression

FT-IR spectroscopy has being a widespread technique in the agro-industry for the quick assess of food components, including the wine. Using the region of wavenumbers 1200–800 cm⁻¹ of the FT-IR spectra wine polysaccharides, Partial Least Squares Regression (PLS1) independent calibration models were built for mannose quantification in complex matrices from white and in red wine extracts. With PLS1 it was not possible to build a calibration model that included both white and red wine extracts. However, a predictive ability of the model for quantification of mannose from mannoproteins based on this FT-IR spectral region was achieved by the application of orthogonal signal correction (OSC)-PLS1.     

Nanoparticle-biomolecular corona: A new approach for the early detection of non-small-cell lung cancer

Lung cancer (LC) is the most common type of cancer and the second cause of death worldwide in men and women after cardiovascular diseases. Non-small-cell lung cancer (NSCLC) is the most frequent type of LC occurring in 85% of cases. Developing new methods for early detection of NSCLC could substantially increase the chances of survival and, therefore, is an urgent task for current research. Nowadays, explosion in nanotechnology offers unprecedented opportunities for therapeutics and diagnosis applications. In this context, exploiting the bio-nano-interactions between nanoparticles (NPs) and biological fluids is an emerging field of research. Upon contact with biofluids, NPs are covered by a biomolecular coating referred to as “biomolecular corona” (BC). In this study, we exploited BC for discriminating between NSCLC patients and healthy volunteers. Blood samples from 10 NSCLC patients and 5 subjects without malignancy were allowed to interact with negatively charged lipid NPs, leading to the formation of a BC at the NP surface. After isolation, BCs were characterized by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). We found that the BCs of NSCLC patients was significantly different from that of healthy individuals. Statistical analysis of SDS-PAGE results allowed discriminating between NSCLC cancer patients and healthy subjects with 80% specificity, 80% sensitivity and a total discriminate correctness rate of 80%. While the results of the present investigation cannot be conclusive due to the small size of the data set, we have shown that exploitation of the BC is a promising approach for the early diagnosis of NSCLC.     

Vitamin C transporter gene (SLC23A1 and SLC23A2) polymorphisms, plasma vitamin C levels, and gastric cancer risk in the EPIC cohort

Vitamin C is known to protect mucosal tissues from oxidative stress and inhibit nitrosamine formation in the stomach. High consumption of fruits, particularly citrus, and higher circulating vitamin C concentrations may be inversely associated with gastric cancer (GC) risk. We investigated 20 polymorphisms in vitamin C transporter genes SCL23A1 and SCL23A2 and GC risk in 365 cases and 1,284 controls nested within the European Prospective Investigation into Cancer and Nutrition cohort. We also evaluated the association between these polymorphisms and baseline plasma vitamin C levels in a subset of participants. Four SNPs were predictors of plasma vitamin C levels (SLC23A1 rs11950646 and rs33972313; SLC23A2 rs6053005 and rs6133175) in multivariable linear regression models. One SNP (SLC23A2 rs6116569) was associated with GC risk, in particular non-cardia GC (OR = 1.63, 95 % CI = 1.11–2.39, based on 178 non-cardia cases), but this association was attenuated when plasma vitamin C was included in the logistic regression model. Haplotype analysis of SLC23A1 yielded no associations with GC. In SLC23A2, one haplotype was associated with both overall and non-cardia GC, another haplotype was associated with GC overall, and a third was associated with intestinal-type GC. Common variants in SLC23A1 and SLC23A2 may influence plasma vitamin C concentration independent of dietary intake, and variation in SLC23A2 may influence GC risk. Additional prospective studies in large populations and consortia are recommended. Investigation of variation in vitamin C transporter genes may shed light on the preventative properties of vitamin C in gastric carcinogenesis.     

Dose-response evaluation of a novel essential oil against Mutans streptococci in vivo

Research has demonstrated the need for identifying a novel antimicrobial agent for topical use in the pediatric dental population. The essential oil of Lippia sidoides Cham. (LSO) has been described as having favorable biological properties, and a broad in vitro and in vivo antimicrobial spectrum against bacteria and yeast infections. Our aim was to determine a dose and formulation of LSO, acceptable for clinical testing in a pediatric population with dental caries. Thirty-seven 6-12-year old children were selected to participate in this study, and randomly allocated to receive different concentrations of either a gel (0.8%, 1%, 1.2% and 1.4%) or a mouth rinse (0.6%, 0.8%, 1% and 1.2%) formulation. The highest percentage MS reduction was observed with 0.8% mouth rinse and 1.4% gel. The efficacy of these concentrations was compared with a Thy-Car mixture formulated as a mouth rinse and gel treatments in 11 children. Saliva was collected after a single application of the antimicrobial treatment to establish effectiveness against MS. Both rinse (p < 0.001) and gel (p = 0.02) formulations produced significant MS reduction. Mouth rinse concentrations above 0.8% were associated with a transient intra-oral burning sensation. In conclusion, mouth rinse and gel LSO formulations demonstrated effectiveness against MS and good acceptance among children. We suggest future randomized clinical trials to test its effectiveness against early childhood caries.     

<Emphasis Type="Italic">Fusarium verticillioides</Emphasis>: Evaluation of Fumonisin Production and Effect of Fungicides on In Vitro Inhibition of Mycelial Growth

The objectives of this study were to evaluate the fumonisin production by 16 F. verticillioides strains on corn cultures and the effect of quintozene and fludioxonil + metalaxyl-M fungicides on “in vitro” mycelial growth on agar. In addition, the effect of fludioxonil + metalaxyl-M on fumonisin production in defined liquid culture medium was analyzed. Fumonisin B₁ levels on corn cultures ranged from 2.41 to 3996.36 μg/g and the F. verticillioides 103F strain produced the highest level (3996.36 ± 390.49 μg/g, P < 0.05). F. verticillioides strains were inoculated in potato dextrose agar with the addition of quintozene (75 to 9,375 μg/ml) and fludioxonil + metalaxyl-M (1.5 + 0.6 to 187.5 + 75 μg/ml) in order to evaluate the effect of these fungicides on “in vitro” mycelial growth. The F. verticillioides strains showed great variability concerning ED₅₀ values, which were below the recommended application dose for quintozene, but above that for fludioxonil + metalaxyl-M. Moreover, fungicide addition to the culture medium increased mean FB₁ levels compared to the control, suggesting the importance of focusing on the effect of fungicides on mycotoxin production as well as on the phytopathogen control.