Fluoride effects on cell viability and ENaC expression in kidney epithelial cells.

Fluoride (F) at micromolar (µM) concentrations induces apoptosis in several cell lines. Moreover, proteomic studies have shown major changes in the profile of proteins involved in signal transduction. These effects may negatively affect ion transport in the kidneys. The activity of epithelial sodium channels (ENaCs) is a limiting factor for sodium and water resorption in the kidneys, which is essential for the maintenance of the electrolyte balance and homeostasis of the body. Here we investigated the effects of F, at different concentrations (10, 40, 100, 200, and 400 µM), on the viability of renal epithelial cells (M-1), and ENaC expression. We showed that sodium fluoride (NaF) reduces cell viability in a concentration-dependent manner (p < 0.05) up to a 96-h time-point when compared to control. Sodium fluoride at moderate concentrations (100 and 200 µM), upregulated the ENaC subunit genes Scnn1a and Scnn1g, but not Scnn1b. Sodium fluoride downregulated all three ENaC subunit genes at a higher concentration of 400 µM (p < 0.05). Immunofluorescence analysis showed that Scnn1a and Scnn1g expression was decreased within 24 h of NaF treatment. After 48 h, NaF (400 µM) increased the expression of Scnn1a but not Scnn1g. However, NaF decreased the expression of Scnn1g at all studied concentrations. We conclude that F, at µM concentrations, modulates the expression of ENaC subunit genes, which is likely to significantly affect molecular signaling in kidney epithelial cells.

The effect of fluoride on the structure, function, and proteome of intestinal epithelia.

Fluoride exposure is widespread, with drinking water commonly containing natural and artificially added sources of the ion. Ingested fluoride undergoes absorption across the gastric and intestinal epithelia. Previous studies have reported adverse gastrointestinal effects with high levels of fluoride exposure. Here, we examined the effects of fluoride on the transepithelial ion transport and resistance of three intestinal epithelia. We used the Caco-2 cell line as a model of human intestinal epithelium, and rat and mouse colonic epithelia for purposes of comparison. Fluoride caused a concentration-dependent decline in forskolin-induced Cl- secretion and transepithelial resistance of Caco-2 cell monolayers, with an IC50 for fluoride of about 3 mM for both parameters. In the presence of 5 mM fluoride, transepithelial resistance fell exponentially with time, with a t1/2 of about 7 hours. Subsequent imaging by immunofluorescence and scanning electron microscopy showed structural abnormalities in Caco-2 cell monolayers exposed to fluoride. The Young's modulus of the epithelium was not affected by fluoride, although proteomic analysis revealed changes in expression of a number of proteins, particularly those involved in cell-cell adhesion. In line with its effects on Caco-2 cell monolayers, fluoride, at 5 mM, also had profound effects on Cl- secretion and transepithelial resistance of both rat and mouse colonic epithelia. Our results show that treatment with fluoride has major effects on the structure, function, and proteome of intestinal epithelia, but only at concentrations considerably higher than those likely to be encountered in vivo, when much lower fluoride doses are normally ingested on a chronic basis.

Population genetic structure of the rock outcrop species Encholirium spectabile (Bromeliaceae): The role of pollination vs. seed dispersal and evolutionary implications.

PREMISE OF THE STUDY: Inselbergs are terrestrial, island-like rock outcrop environments that present a highly adapted flora. The epilithic bromeliad Encholirium spectabile is a dominant species on inselbergs in the Caatinga of northeastern Brazil. We conducted a population genetic analysis to test whether the substantial phenotypic diversity of E. spectabile could be explained by limited gene flow among populations and to assess the relative impact of pollen vs. seed dispersal on the genetic structure of the species. METHODS: Nuclear and chloroplast microsatellite markers were used to genotype E. spectabile individuals from 20 rock outcrop locations, representing four geographic regions: northern Espinhaço Range, Borborema Plateau, southwestern Caatinga and southeastern Caatinga. F-statistics, structure, and other tools were applied to evaluate the genetic makeup of populations. KEY RESULTS: Considerable levels of genetic diversity were revealed. Genetic structuring among populations was stronger on the plastid as compared with the nuclear level, indicating higher gene flow via bat pollination as compared with seed dispersal by wind. structure and AMOVA analyses of the nuclear data suggested a high genetic differentiation between two groups, one containing all populations from the southeastern Caatinga and the other one comprising all remaining samples. CONCLUSIONS: The strong genetic differentiation between southeastern Caatinga and the remaining regions may indicate the occurrence of a cryptic species in E. spectabile. The unique genetic composition of each inselberg population suggests in situ conservation as the most appropriate protection measure for this plant lineage.

The effect of fluoride on the structure, function, and proteome of a renal epithelial cell monolayer.

High concentrations of fluoride in the body may cause toxic effects. Here, we investigated the effects of fluoride on the structure, function, and proteome of a cortical collecting duct epithelium in vitro. Kidney tubule cells (M-1) were chosen because the concentration of fluoride in the kidney is 4-5-fold higher than that in plasma. Mouse M-1 cell monolayers were incubated in fluoride-containing media, and the amiloride-sensitive short-circuit current and transepithelial resistance were measured. The Young's modulus of the epithelium was determined using atomic force microscopy, and the effect of fluoride on epithelial structure was assessed using scanning and transmission electron microscopy, and immunofluorescence. Differences in the expression of membrane proteins were evaluated using proteomics and bioinformatics. Fluoride exposure reduced both transepithelial Na+ transport and resistance. The IC50 for fluoride was ∼300 µM for both effects, and the half-times for the decays of ion transport and resistance were 8.4 h and 3.6 days, respectively. Fluoride treatment did not affect the sensitivity of Na+ transport to amiloride. The Young's modulus of the epithelium was also unaffected by fluoride; however, the functional effects of fluoride were accompanied by marked structural effects. Proteomic analysis revealed changes in expression of a number of proteins, and particularly mitochondrial proteins. Treatment with fluoride had profound effects on the structure, function and proteome of a model cortical collecting duct epithelium. Significantly, however, these effects were produced only at concentrations considerably higher than those likely to be encountered in vivo. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1455-1467, 2017.

Higher level of IL-6 in Jaccoud's arthropathy secondary to systemic lupus erythematosus: a perspective for its treatment?

Jaccoud's arthropathy (JA) is a condition characterized clinically by 'reversible' joint deformities along with an absence of articular erosions on a plain radiograph. The main clinical entity associated with JA is systemic lupus erythematosus (SLE) with a prevalence of around 5 %. The aim of the present study was to compare the inflammatory markers including cytokine levels in blood of SLE patients with and without JA. Patients with diagnosis of SLE as defined by ACR criteria were screened and divided in two groups, one with JA and one control group without JA. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), complement C3 and C4 levels antinuclear antibodies (ANA), anti-dsDNA antibodies and serum levels of IL-2, IL-6, IL-10, IL-21, IL-22 and TNF-α were determined in all patients. Eighty female patients with SLE, 18 (22.5 %) with JA and 62 (77.5 %) without JA, were included in this study. JA patients had higher disease duration (p = 0.008), ESR (p < 0.001), CRP level (p = 0.002), ANA titer (p < 0.001) and dsDNA antibody level (p = 0.009). The serum levels of IL-2, IL-10, IL-21, IL-22 and TNF-α were not significantly different between the two groups (p > 0.05), but the level of IL-6 was higher in JA group (p < 0.001). The serum level of IL-6 might have a correlation with JA secondary to SLE.

Tracking new insights into antifungal and anti-mycotoxigenic properties of a biofilm forming Pediococcus pentosaceus strain isolated from grain silage.

The present study offers detailed insights into the antifungal and anti-mycotoxigenic potential of a biofilm forming lactic acid bacterium (Pediococcus pentosaceus) against one atoxigenic (Aspergillus flavus) and two toxigenic (Aspergillus nomius and Fusarium verticillioides) fungal strains. The antifungal effect of P. pentosaceus LBM18 strain was initially investigated through comparative analysis of fungi physiology by macroscopic visual evaluations and scanning electron microscopy examinations. The effects over fungal growth rate and asexual sporulation were additionally accessed. Furthermore, analytical evaluations of mycotoxin production were carried out by HPLC-MS/MS to provide insights on the bacterial anti-mycotoxigenic activity over fungal production of the aflatoxins B1, B2, G1 and G2 as well as fumonisins B1 and B2. Finally, reverse transcription quantitative real-time PCR (RT-qPCR) analysis was employed at the most effective bacterial inoculant concentration to evaluate, at the molecular level, the down-regulation of genes aflR, aflQ and aflD, related to the biosynthesis of aflatoxins by the strain of Aspergillus nomius. The effects over mycotoxin contamination were thought to be result of a combination of several biotic and abiotic factors, such as interaction between living beings and physical-chemical aspects of the environment, respectively. Several possible mechanisms of action were addressed along with potentially deleterious effects ascribing from P. pentosaceus misuse as biopesticide, emphasizing the importance of evaluating lactic acid bacteria safety in new applications, concentrations, and exposure scenarios.

Higher number of Helicobacter pylori CagA EPIYA C phosphorylation sites increases the risk of gastric cancer, but not duodenal ulcer.

BACKGROUND: Helicobacter pylori infection is one of the most common infections worldwide and is associated with gastric cancer and peptic ulcer. Bacterial virulence factors such as CagA have been shown to increase the risk of both diseases. Studies have suggested a causal role for CagA EPIYA polymorphisms in gastric carcinogenesis, and it has been shown to be geographically diverse. We studied associations between H. pylori CagA EPIYA patterns and gastric cancer and duodenal ulcer, in an ethnically admixed Western population from Brazil. CagA EPIYA was determined by PCR and confirmed by sequencing. A total of 436 patients were included, being 188 with gastric cancer, 112 with duodenal ulcer and 136 with gastritis. RESULTS: The number of EPIYA C segments was significantly associated with the increased risk of gastric carcinoma (OR=3.08, 95% CI=1.74 to 5.45, p<10-3) even after adjustment for age and gender. Higher number of EPIYA C segments was also associated with gastric atrophy (p=0.04) and intestinal metaplasia (p=0.007). Furthermore, patients infected by cagA strains possessing more than one EPIYA C segment showed decreased serum levels of pepsinogen I in comparison with those infected by strains containing one or less EPIYA C repeat. Otherwise, the number of EPIYA C segments did not associate with duodenal ulcer. CONCLUSIONS: Our results demonstrate that infection with H. pylori strains harbouring more than one CagA EPIYA C motif was clearly associated with gastric cancer, but not with duodenal ulcer.Higher number of EPIYA C segments was also associated with gastric precancerous lesions as demonstrated by histological gastric atrophic and metaplastic changes and decreased serum levels of pepsinogen I.

Synthesis of chitosan-lysozyme microspheres, physicochemical characterization, enzymatic and antimicrobial activity.

Chitosan microspheres (CMS) by the emulsion-chemical cross-linking method with and without lysozyme immobilization were synthesized and characterized. The technique conditions were adjusted, and spherical particles with approximate diameters of 3.74 ± 1.08 µm and 0. 29 ± 0.029 µm to CMS and chitosan-lysozyme microspheres (C-LMS), respectively, were obtained. The microspheres were characterized by scanning electron microscopy (FESEM), Spectroscopy Fourier Transform Spectroscopy (ATR-FTIR), X-ray diffraction (XRD), and zeta potential. Particle size was identified by laser light scattering (DLS) and the thermal properties by Differential Scanning Calorimetry (DSC) and Thermogravimetry (TGA) were determined. By the lysis of Micrococcus lysodeikticus, the activity of the microspheres was determined, and the results correlated with the amount of lysozyme used in the immobilization process and the enzyme loading efficiency was 67%. Finally, release tests pointed out the amount of enzyme immobilized on the microsphere surface. These results showed that chitosan microspheres could be used as material for lysozyme immobilization by cross-linking technique. The antimicrobial activity was tested by inhibition percent determination, and it evidenced both chitosan microspheres (CMS) and chitosan-lysozyme microspheres (C-LMS) positive antimicrobial activity to Staphylococcus aureus, Enterococcus faecalis and Pseudomonas aeruginosa.

Characterization of levan produced by a Paenibacillus sp. isolated from Brazilian crude oil.

A levan-type fructooligosaccharide was produced by a Paenibacillus strain isolated from Brazilian crude oil, the purity of which was 98.5% after precipitation with ethanol and dialysis. Characterization by FTIR, NMR spectroscopy, GC-FID and ESI-MS revealed that it is a mixture of linear ß(2 â†’ 6) fructosyl polymers with average degree of polymerization (DP) of 18 and branching ratio of 20. Morphological structure and physicochemical properties were investigated to assess levan microstructure, degradation temperature and thermomechanical features. Thermal Gravimetric Analysis highlighted degradation temperature of 218 °C, Differential Scanning Calorimetry (DSC) glass transition at 81.47 °C, and Dynamic Mechanical Analysis three frequency-dependent transition peaks. These peaks, corresponding to a first thermomechanical transition event at 86.60 °C related to the DSC endothermic event, a second at 170.9 °C and a third at 185.2 °C, were attributed to different glass transition temperatures of oligo and polyfructans with different DP. Levan showed high morphological versatility and technological potential for the food, nutraceutical, and pharmaceutical industries.

Cellular, physiological and molecular approaches to investigate the antifungal and anti-aflatoxigenic effects of thyme essential oil on Aspergillus flavus.

Several approaches, including the detection of apoptotic-like cell death, aflatoxin B1 (AFB1) production and gene expression analysis, were carried out to provide insights into the antifungal and anti-aflatoxigenic effects of thyme essential oil (EO) on Aspergillus flavus. At 0.5 µL mL-1, thyme EO completely inhibited A. flavus growth. Furthermore, this antifungal activity triggered significant apoptosis, via nuclear condensation (87.5% of nuclei analyzed) and plasma membrane damage (in 100% of treated hyphae). Further analysis of AFB1 production and gene expression related to secondary metabolism (laeA) and the mechanism of virulence (lipA and meT) of A. flavus in the presence of thyme EO indicated important physiological changes related to its anti-aflatoxigenic property. These results highlight the potent antifungal abilities of thyme EO in controlling A. flavus and AFB1 production, especially the abilities that operate by exerting changes at the molecular level and inducing significant apoptotic-like cell death.

Effect of temperature on growth, gene expression, and aflatoxin production by Aspergillus nomius isolated from Brazil nuts.

Aspergillus nomius is a potent producer of aflatoxins B and G and is one of the most common species of fungi found in Brazil nuts. Temperature is considered a major abiotic factor that influences fungal colonization and aflatoxin production in nuts during pre- and post-harvest. Therefore, assessment of the response of aflatoxigenic species to different temperatures is important to add information about the understanding of aflatoxin production by Aspergillus nomius and may help in the development of new strategies to prevent aflatoxin contamination. The aim of this study was to evaluate the effect of temperature (25, 30, and 35 °C) on the radial growth, aflatoxin production (B and G), and aflatoxin gene expression of seven A. nomius strains isolated from Brazil nuts. The optimal temperature for growth was 30 °C and was also the best condition for the expression of the aflR, aflD, and aflQ genes. However, maximum production of aflatoxins B and G occurred at 25 °C. Interestingly, high expression of the structural gene aflQ was observed in the maximum aflatoxin production condition (25 °C). The present study demonstrates that temperature may influence aflatoxin production by A. nomius. The combination of molecular and physiological data aids the understanding of the aflatoxigenic species response to different temperatures and can assist in predicting the driving environmental factors that influence aflatoxin contamination of Brazil nuts.

Bromelain immobilization in cellulose triacetate nanofiber membranes from sugarcane bagasse by electrospinning technique.

Cellulose triacetate (CTAB) synthesized by cellulose extracted from sugarcane bagasse, and commercial cellulose acetate (CA) were used to produce nanofiber membranes contained bromelain by electrospinning technique. About 1.3 g of cellulose acetate per gram of bagasse were obtained, and both CTAB and CA was characterized by analysis of Fourier Transform Infrared Spectroscopy (FTIR) and Differential Scanning Calorimetry (DSC). The nanofiber membranes were produced by electrospinning process testing the following conditions: voltage 25 kV, flow rate 4 mL/h and distance 10 cm, using acetone/ dimethylformamide (DMF) (85:15 m/ m) to 15% cellulose triacetate (70% CA + 30% CTAB) or CA solutions. Scanning Electron Microscopy (SEM) was used to nanofiber membranes characterization. Bromelain was immobilized on the nanofiber membranes by crosslinking with glutaraldehyde and directly in the electrospinning step, the highest activity recovery was about 675% and in vitro controlled release tests were performed to semi-quantitatively evaluate the release of the enzyme bromelain thus demonstrating complete release process in 3 days.

Wettability and pre-osteoblastic behavior evaluations of a dense bovine hydroxyapatite ceramics.

In this study, the wettability, cell viability, and roughness of an experimental dense bovine hydroxyapatite [Ca10(PO4)6(OH)2] ceramic block were evaluated so that, in the future, it could be used as a base material for dental implants. The results to commercial zirconia and a commercially pure titanium (Ti) alloy were compared. The surface roughness and contact angles were measured. An in vitro evaluation was conducted by means of tests in which pre-osteoblastic MC3T3-E1 cells were placed in indirect and direct contact with these materials. For cell viability, a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and crystal violet test were conducted. A qualitative analysis was conducted using variable pressure scanning electron microscopy (SEM). No statistically significant differences were observed in wettability and roughness tests among the groups. In both the MTT assay and crystal violet test, all groups demonstrated satisfactory results without cytotoxicity. SEM showed cell adhesion and cell proliferation results on the material surfaces after 24 h and 48 h. In conclusion, this dense Ca10 (PO4)6(OH)2 ceramic can be considered as a potential biocompatible material.

Vanadium ionic species from degradation of Ti-6Al-4V metallic implants: In vitro cytotoxicity and speciation evaluation.

Among the metallic materials used in biomedical industry, the most common choice for orthopedics and dental implants is titanium (Ti) and its alloys, mainly due to their superior corrosion and tribocorrosion resistance and biocompatibility. Under different conditions in vivo, such as different pH levels, composition of body fluid and mechanical loads, metallic materials may suffer from degradation, resulting in the release of undesired wear particles and ions. In particular, the Ti-6Al-4V system represents almost half of the production of Ti as a biomaterial and many concerns have been raised about titanium, aluminum and vanadium ions releasing. This work evaluates the cytotoxic effects of vanadium ionic species generated from Ti-6Al-4V surfaces regarding mouse pre-osteoblasts and fibroblasts. In our cell viability tests, we noticed a significant decrease in the fibroblasts' cell viability with vanadium concentrations (23 µM) close to those previously reported to be observed in vivo in patients with poor functioning of their medical devices based on Ti-6Al-4V (30 µM). Speciation modelling was carried-out, for the first time, to this system. Results of the modelling reveal that vanadates(V), namely H2VO4- and HVO42-, are the main species present in cell culture media. Otherwise, in synovial fluids of individuals with poorly functioning implants, wherein the concentration of vanadium may go up to ca. 30 µM, the tentative theoretical speciation data indicates a high occurrence probability for VV- and VIV-species bound to albumin and hyaluronic acid. In conclusion, even though relatively low concentrations of vanadium may be released from Ti-6Al-4V implants in vivo, the continuous contact with peri-implant cells for long periods of time may represent a potentially hazardous situation.

A morphological, enzymatic and metabolic approach to elucidate apoptotic-like cell death in fungi exposed to h- and α-molybdenum trioxide nanoparticles.

The present study compares for the first time the effects of h-MoO3 and α-MoO3 against two fungal strains: Aspergillus niger and Aspergillus flavus. The h-MoO3 nanoparticles were more toxic to both fungi than α-MoO3. The toxic effects of h-MoO3 were more pronounced toward A. flavus, which presented a growth inhibition of 67.4% at 200 mg L-1. The presence of the nanoparticles affected drastically the hyphae morphology by triggering nuclear condensation and compromising the hyphae membrane. Further analysis of the volatile organic compounds (VOCs) produced by both fungi in the presence of the nanomaterials indicated important metabolic changes related to programmed cell death. These nanomaterials induced the production of specific antifungal VOCs, such as ß-Elemene and t-Cadinol, by the fungi. The production of essential enzymes involved in fungal metabolism, such as acid phosphatase, naphthol-As-BI-phosphohydrolase, ß-galactosidase, ß-glucosidase and N-acetyl-ß-glucosaminidase, reduced significantly in the presence of the nanomaterials. The changes in enzymatic production and VOCs corroborate the fact that these nanoparticles, especially h-MoO3, exert changes in the fungal metabolism, triggering apoptotic-like cell death responses in these fungi.

Influence of environmental factors on tenuazonic acid production by Epicoccum sorghinum: An integrative approach of field and laboratory conditions.

Sorghum is the fifth most cultivated and consumed grain in the world. However, this grain is frequently contaminated with toxins from fungi. The present study evaluated the effects of environmental factors on tenuazonic acid (TeA) production by Epicoccum sorghinum in the field and in controlled laboratory conditions. In this study, 50 sorghum grain samples were collected from summer and autumn growing seasons and analyzed for TeA contamination using LC-MS/MS. To further understand the ecophysiology of this fungus, an isolated strain of E. sorghinum from the field was investigated for its development and TeA production under controlled environmental conditions in the laboratory. In the ecophysiological investigation, the effects of water activity (0.90, 0.95, 0.99) and temperature (18, 22, 26 and 30 °C) were evaluated on the radial growth, enzymatic production and expression of TAS1, which is the gene involved in TeA production. Results showed that in the field, the summer season presented the highest TeA average level in the grains (587.8 µg/kg) compared to level found in the autumn (440.5 µg/kg). The ecophysiological investigation confirmed that E. sorghinum produces more actively TeA under environmental conditions simulating the summer season. Optimum growth, maximum TAS1 gene expression, and higher extracellular enzymatic production were observed at 26 °C with a water activity of 0.99. Pearson correlation analyses showed that the production of TeA highly correlates with fungal growth. The present study demonstrates that abiotic factors in a combined approach of field and laboratory conditions will assist in predicting the driving environmental factors that could affect growth of E. sorghinum and TeA production in sorghum grains.

Clinical and laboratory aspects of dyslipidemia in Brazilian women with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is associated with dyslipidemia, atherosclerosis, and cardiovascular disease. In this study, we investigated the presence of dyslipidemia in Brazilian SLE patients by evaluating their lipid profile and immune status, including the production of autoantibodies and cytokines involved in atherogenesis. Ninety-four female SLE patients participated in this study and, based on their lipid profile, were classified as dyslipidemic or not. All were tested for antinuclear antibodies (ANAs), antiphospholipid antibodies, and autoantibodies to extractable nuclear antigens and double-stranded DNA. Serum levels of apolipoproteins A and B, C3, C4, and C-reactive protein were measured, as well as serum levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-10. Lupus activity was scored according to the Systemic Lupus Erythematosus Disease Activity Index 2000. Sixty-nine patients (73.4%) had dyslipidemia, and the remaining 25 patients (26.6%) were non-dyslipidemic. Lupus activity was correlated with non-high-density lipoprotein cholesterol and triglyceride (TG) levels (non-HDL-C, r = 0.34 and p = 0.0043 and r = 0.46 and p < 0.0001, respectively). Atherogenic indexes apolipoprotein B/apolipoprotein A and TG:HDL-C ratios were higher in dyslipidemic women, and TG:HDL was correlated with disease activity (r = 0.40, p = 0.0007). IL-6, TNF-α, and IL-10 levels were similar between groups; however, a positive correlation between IL-6 and CRP levels was only observed in the group with dyslipidemia (r = 0.55, p < 0.0001). Female Brazilian SLE patients present a high prevalence of dyslipidemia and exhibit a higher risk of cardiovascular diseases as compared with female SLE patients without dyslipidemia and healthy individuals.

Emerging Role of HMGB1 in the Pathogenesis of Schistosomiasis Liver Fibrosis.

In chronic schistosomiasis, liver fibrosis is linked to portal hypertension, which is a condition associated with high mortality and morbidity. High mobility group box 1 (HMGB1) was originally described as a nuclear protein that functions as a structural co-factor in transcriptional regulation. However, HMGB1 can also be secreted into the extracellular milieu under appropriate signal stimulation. Extracellular HMGB1 acts as a multifunctional cytokine that contributes to infection, injury, inflammation, and immune responses by binding to specific cell-surface receptors. HMGB1 is involved in fibrotic diseases. From a clinical perspective, HMGB1 inhibition may represent a promising therapeutic approach for treating tissue fibrosis. In this study, we demonstrate elevated levels of HMGB1 in the sera in experimental mice or in patients with schistosomiasis. Using immunohistochemistry, we demonstrated that HMGB1 trafficking in the hepatocytes of mice suffering from acute schistosomiasis was inhibited by Glycyrrhizin, a well-known HMGB1 direct inhibitor, as well as by DIC, a novel and potential anti-HMGB1 compound. HMGB1 inhibition led to significant downregulation of IL-6, IL4, IL-5, IL-13, IL-17A, which are involved in the exacerbation of the immune response and liver fibrogenesis. Importantly, infected mice that were treated with DIC or GZR to inhibit HMGB1 pro-inflammatory activity showed a significant increase in survival and a reduction of over 50% in the area of liver fibrosis. Taken together, our findings indicate that HMGB1 is a key mediator of schistosomotic granuloma formation and liver fibrosis and may represent an outstanding target for the treatment of schistosomiasis.

Titanium dioxide nanotubes addition to self-adhesive resin cement: Effect on physical and biological properties.

OBJECTIVES: This study has investigated the influence of Titanium dioxide nanotubes (TiO2-nt) addition to self-adhesive resin cement on the degree of conversion, water sorption, and water solubility, mechanical and biological properties. METHODS: A commercially available auto-adhesive resin cement (RelyX U200™, 3M ESPE) was reinforced with varying amounts of nanotubes (0.3, 0.6, 0.9wt%) and evaluated at different curing modes (self- and dual cure). The DC in different times (3, 6, 9, 12 and 15min), water sorption (Ws) and solubility (Sl), 3-point flexural strength (σf), elastic modulus (E), Knoop microhardness (H) and viability of NIH/3T3 fibroblasts were performed to characterize the resin cement. RESULTS: Reinforced self-adhesive resin cement, regardless of concentration, increased the DC for the self- and dual-curing modes at all times studied. The concentration of the TiO2-nt and the curing mode did not influence the Ws and Sl. Regarding σf, concentrations of both 0.3 and 0.9wt% for self-curing mode resulted in data similar to that of dual-curing unreinforced cement. The E increased with the addition of 0.9wt% for self-cure mode and H increased with 0.6 and 0.9wt% for both curing modes. Cytotoxicity assays revealed that reinforced cements were biocompatible. SIGNIFICANCE: TiO2-nt reinforced self-adhesive resin cement are promising materials for use in indirect dental restorations. Taken together, self-adhesive resin cement reinforced with TiO2-nt exhibited physicochemical and mechanical properties superior to those of unreinforced cements, without compromising their cellular viability.

Draft Genome Sequence of Sorghum Grain Mold Fungus Epicoccum sorghinum, a Producer of Tenuazonic Acid.

The facultative plant pathogen Epicoccum sorghinum is associated with grain mold of sorghum and produces the mycotoxin tenuazonic acid. This fungus can have serious economic impact on sorghum production. Here, we report the draft genome sequence of E. sorghinum (USPMTOX48).