Anticlastogenic effect of β-glucan, extracted from Saccharomyces cerevisiae, on cultured cells exposed to ultraviolet radiation

β-glucan is an important polysaccharide due to its medicinal properties of stimulating the immune system and preventing chronic diseases such as cancer. The aim of the present study was to determine the anticlastogenic effect of β-glucan in cells exposed to ultraviolet radiation (UV). Chromosome aberration assay was performed in drug-metabolizing cells (HTC) and non drug-metabolizing cells (CHO-K1 and repair-deficient CHO-xrs5), using different treatment protocols. Continuous treatment (UV + β-glucan) was not effective in reducing the DNA damage only in CHO-xrs5 cells. However, the pre-treatment protocol (β-glucan before UV exposition) was effective in reducing DNA damage only in CHO-K1 cells. In post-treatment (β-glucan after UV exposition) did not show significative anticlastogenic effects, although there was a tendency toward prevention. The data suggest that β-glucan has more than one action mechanism, being capable of exerting desmutagenic as well as bio-antimutagenic action. The findings also suggest that the presence of the xenobiotic metabolizing system can reduce the chemopreventive capacity of β-glucan. Therefore, these results indicate that β-glucan from Saccharomyces cerevisiae can be used in the prevention and/or reduction of DNA damage.     

Mutation analysis of GJB2 and GJB6 genes in Southeastern Brazilians with hereditary nonsyndromic deafness

In developed countries deafness has a genetic cause in over 60% of the cases. Contrastingly, in Brazil, it is estimated that only 16% of all deafnesses are caused by genetic factors. Among hereditary hearing deficiencies, approximately half is caused by mutations in the Gap Junction Protein Beta-2 (GJB2) gene, which encodes the protein Connexin 26 (Cx26). There are four mutations in this gene that present high prevalence in specific ethnical groups, namely, 35delG, 167delT, 235delC, and W24X. The 35delG mutation is the most frequent one, occurring in homozygosity or in compound heterozygosity with mutations in the GJB2 and GJB6 genes. This study aims to determine the prevalence of GJB2-35delG, GJB2-167delT, GJB2-235delC, GJB2-W24X, del (GJB6-D13S1830), and del (GJB6-D13S1854) mutations in patients with nonsyndromic deafness in the Espirito Santo State, Brazil. A total of 77 individuals were evaluated, from which 88.3% presented normal genotypes for all analyzed mutations, 1.3% were compound heterozygotes for 35delG-GJB2/D13S1830-GJB6, 1.3% were compound heterozygotes for 35delG/D13S1854-GJB6, 3.9% were homozygotes for the 35delG mutation and 5.2% were heterozygotes for 35delG/GJB2. The frequency of mutant alleles 35delG/GJB2, del (D13S1830/GJB6), and del (D13S1854/GJB6) was 7.8, 0.65, and 0.65%, respectively. Mutations 167delT, 235delC, and W24X were not detected. Determining the prevalence of specific mutations related to inherited deafness in a population can contribute to the development of more efficient and affordable molecular diagnostic protocols, and help in the genetic counseling of patients and their families.     

Expression of microRNAs miR-21 and miR-326 associated with HIF-1α regulation in neurospheres of glioblastoma submitted to ionizing radiation treatment

BackgroundGlioblastoma is an incurable neoplasm. Its hypoxia mechanism associated with cancer stem cells (CSCs) demonstrates hypoxia-inducible factor 1α (HIF-1α) expression regulation, which is directly related to tumor malignancy. The aim of this study was to identify a possible tumor malignancy signature associated with regulation of HIF-1α by microRNAs miR-21 and miR-326 in the subpopulation of tumor stem cells which were irradiated by ion in primary culture of patients diagnosed with glioblastoma.Materials and methodsWe used cellular cultures from surgery biopsies of ten patients with glioblastoma. MicroRNA expressions were analyzed through real-time polymerase chain reaction (PCR ) and correlated with mortality and recurrence. The ROC curve displayed the cutoff point of the respective microRNAs in relation to the clinical prognosis, separating them by group.ResultsThe miR-21 addressed high level of expression in the irradiated neurosphere group (p = 0.0028). However, miR-21 was not associated with recurrence and mortality. miR-326 can be associated with tumoral recurrence (p = 0.032) in both groups; every 0.5 units of miR-326 increased the chances of recurrence by 1,024 (2.4%).ConclusionThe high expression of miR-21 in the irradiated group suggests its role in the regulation of HIF-1α and in the radioresistant neurospheres. miR-326 increased the chances of recurrence in both groups, also demonstrating that positive regulation from miR-326 does not depend on ionizing radiation treatment.     

Ecto-5'-nucleotidase/CD73 inhibition by quercetin in the human U138MG glioma cell line

Gliomas are the most malignant of the primary brain tumors. Nucleotides represent an important class of extracellular molecules that are crucial for the normal function of the nervous system. ATP and adenosine can stimulate cell proliferation in different glioma cell lines; the events induced by extracellular adenine nucleotides are controlled by the action of ecto-nucleotidases, which hydrolyze ATP into adenosine in the extracellular space. Recent studies have shown that quercetin has an anti-proliferative effect on the U138MG glioma cell line. Since evidence suggests that purinergic signaling is involved in the growth and progression of glioma and, taking into consideration the anti-proliferative effect elicited by quercetin in this tumor type, the aim of the present study was to better investigate the extracellular metabolism of AMP and evaluate the effect of quercetin on this system in the human U138MG glioma cell line. The adenine products secreted by glioma cells were first characterized; extracellular AMP was efficiently metabolized by the glioma culture, demonstrating a very active ecto-5'-NT/CD73. Quercetin was able to inhibit the ecto-5'-NT/CD73 activity and modulate its expression. In addition, the cell treatment with APCP (alpha,beta-methyleneadenosine-5'-diphosphate), an ecto-5'-NT/CD73 inhibitor, led to a significant reduction in glioma cell proliferation. We suggest that the inhibition of ecto-5'-NT/CD73 may result in a decrease in extracellular adenosine production with a consequent reduction in tumor progression.     

Exploring N-Acylhydrazone Derivatives Against Clinical Resistant Bacterial Strains

Bacterial multiresistance is a health problem worldwide that demands new antimicrobials for treating bacterial-related infections. In this study, we evaluated the antimicrobial activity and the theoretical toxicology profile of N-substituted-phenylamino-5-methyl-1H-1,2,3-triazole-4-carbohydrazide derivatives against gram-positive and gram-negative bacteria clinical strains. On that purpose we determined the minimum inhibitory (MIC) and bactericidal (MBC) concentrations, the in vitro cytotoxicity, and in silico risk profiles, also comparing with antimicrobial agents of clinical use. Among the 16 derivatives analyzed, four nitrofurans (N–H–FUR–NO₂, N–Br–FUR–NO₂, N–F–FUR–NO₂, N–Cl–FUR–NO₂) showed promising MIC and MBC values (MIC = MBC = 1–16 μg/mL). The experimental data revealed the potential of these derivatives, which were comparable to the current antimicrobials with similar bactericidal and bacteriostatic profiles. Therefore, these molecules may be feasible options to be explored for treating infections caused by multiresistant strains. Our in vitro and in silico toxicity reinforced these results as these derivatives presented low cytotoxicity against human macrophages and low theoretical risk profile for irritant and reproductive effects compared to the current antimicrobials (e.g., vancomycin and ciprofloxacin). The molecular modeling analysis also revealed positive values for their theoretical druglikeness and drugscore. The presence of a 5-nitro-2-furfur-2-yl group seems to be essential for the antimicrobial activity, which pointed these acylhydrazone derivatives as promising for designing more potent and safer compounds.     

Elucidating the mechanism of poricidal anther dehiscence in Miconia species (Melastomataceae)

Melastomataceae have porate anthers. However, unlike Solanaceae and many monocots, in which the poricidal dehiscence depends on the presence of a mechanical layer (often the endothecium), most members of Melastomataceae have no evident specialized layer related to the poricidal opening. The goal of this study was to characterize the tissues that form the apical pore of the anther in 10 Miconia species, which may help to understand the nearly unknown mechanism of anther dehiscence in this genus, considered to be one of the largest and most diverse New World genera. Before anthesis, the apical pores of all of the species are closed by a uniseriate epidermis, the cells of which lack a cuticle. In contrast, the epidermis of the remainder of the anther is covered by a thick, ornamented cuticle. Among Myrtales, the Melastomataceae form a clade with Alzateaceae, Crypteroniaceae and Penaeaceae, almost all of which have anthers with endothecium lacking wall thickenings. In these families, the endothecium may or may not be present in the mature anther, with degenerating cells in the latter case. Anther dehiscence does not depend on the endothecium as the mechanical layer, and this process is still not well understood. However, in the Miconia species studied here, the cuticle may prevent tissue dehydration, and the pore opening seems to be due to the passive process of dehydration taking place only in the pore region due to the absence of the cuticle.     

Drinking Patterns and Alcohol Use Disorders in S?o Paulo,Brazil: The Role of Neighborhood Social Deprivation and Socioeconomic Status

Background

Research conducted in high-income countries has investigated influences of socioeconomic inequalities on drinking outcomes such as alcohol use disorders (AUD), however, associations between area-level neighborhood social deprivation (NSD) and individual socioeconomic status with these outcomes have not been explored in Brazil. Thus, we investigated the role of these factors on drink-related outcomes in a Brazilian population, attending to male-female variations.

Methods

A multi-stage area probability sample of adult household residents in the São Paulo Metropolitan Area was assessed using the WHO Composite International Diagnostic Interview (WMH-CIDI) (n = 5,037). Estimation focused on prevalence and correlates of past-year alcohol disturbances [heavy drinking of lower frequency (HDLF), heavy drinking of higher frequency (HDHF), abuse, dependence, and DMS-5 AUD] among regular users (RU); odds ratio (OR) were obtained.

Results

Higher NSD, measured as an area-level variable with individual level variables held constant, showed an excess odds for most alcohol disturbances analyzed. Prevalence estimates for HDLF and HDHF among RU were 9% and 20%, respectively, with excess odds in higher NSD areas; schooling (inverse association) and low income were associated with male HDLF. The only individual-level association with female HDLF involved employment status. Prevalence estimates for abuse, dependence, and DSM-5 AUD among RU were 8%, 4%, and 8%, respectively, with excess odds of: dependence in higher NSD areas for males; abuse and AUD for females. Among RU, AUD was associated with unemployment, and low education with dependence and AUD.

Conclusions

Regular alcohol users with alcohol-related disturbances are more likely to be found where area-level neighborhood characteristics reflect social disadvantage. Although we cannot draw inferences about causal influence, the associations are strong enough to warrant future longitudinal alcohol studies to explore causal mechanisms related to the heterogeneous patterns of association and male-female variations observed herein. Hopefully, these findings may help guide future directions for public health.     

Autophagy is decreased in mesenteric fat tissue but not in intestinal mucosae of patients with Crohn’s disease

Crohn??s disease (CD) is a chronic intestinal disease with a multifactorial etiology. Recently, a role for mesenteric fat has been proposed in CD pathophysiology, since fat hypertrophy is detected close to the affected intestinal area; however, there are few studies regarding autophagy and the hypertrophied mesenteric tissue in CD. To evaluate autophagy-related proteins in intestinal mucosae and mesenteric fat of patients with CD and controls, patients with ileocecal CD (CD Group) and with non-inflammatory disease (FC Group) selected for surgery were studied. Expression of LC3-II was determined by immunoblotting of protein extracts. In addition, beclin-1, LC3 and Atg16-L1 RNA levels were measured using RT-PCR. The expression of LC3-II was significantly lower in the mesenteric tissue and higher in intestinal mucosae of CD when compared to controls. However, mRNA expression of autophagy-related proteins was similar when comparing the mesenteric fat groups. These findings suggest a defect in autophagy activation in the mesenteric fat tissue of CD individuals, which could be involved in the maintenance of the inflammatory process.     

Weissella: An Emerging Bacterium with Promising Health Benefits

Weissella strains have been the subject of much research over the last 5 years because of the genus’ technological and probiotic potential. Certain strains have attracted the attention of the pharmaceutical, medical, and food industries because of their ability to produce antimicrobial exopolysaccharides (EPSs). Moreover, Weissella strains are able to keep foodborne pathogens in check because of the bacteriocins, hydrogen peroxide, and organic acids they can produce; all listed have recognized pathogen inhibitory activities. The Weissella genus has also shown potential for treating atopic dermatitis and certain cancers. W. cibaria, W. confusa, and W. paramesenteroides are particularly of note because of their probiotic potential (fermentation of prebiotic fibers) and their ability to survive in the gastrointestinal tract. It is important to note that most of the Weissella strains with these health-promoting properties have been shown to be save safe, due to the absence or the low occurrence of virulence or antibiotic-resistant genes. A large number of scientific studies continue to report on and to support the use of Weissella strains in the food and pharmaceutical industries. This review provides an overview of these studies and draws conclusions for future uses of this rich and previously unexplored genus.

     

Population Genetic Structure of the Magnificent Frigatebird Fregata magnificens (Aves,Suliformes) Breeding Colonies in the Western Atlantic Ocean

The Magnificent Frigatebird Fregata magnificens has a pantropical distribution, nesting on islands along the Atlantic and Pacific coasts. In the Caribbean, there is little genetic structure among colonies; however, the genetic structure among the colonies off Brazil and its relationship with those in the Caribbean are unknown. In this study, we used mtDNA and microsatellite markers to infer population structure and evolutionary history in a sample of F. magnificens individuals collected in Brazil, Grand Connétable (French Guyana), and Barbuda. Virtually all Brazilian individuals had the same mtDNA haplotype. There was no haplotype sharing between Brazil and the Caribbean, though Grand Connétable shared haplotypes with both regions. A Bayesian clustering analysis using microsatellite data found two genetic clusters: one associated with Barbuda and the other with the Brazilian populations. Grand Connétable was more similar to Barbuda but had ancestry from both clusters, corroborating its “intermediate” position. The Caribbean and Grand Connétable populations showed higher genetic diversity and effective population size compared to the Brazilian population. Overall, our results are in good agreement with an effect of marine winds in isolating the Brazilian meta-population.