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Background: Germ cell tumors (GCTs) comprise a rare and heterogeneous group of neoplasms presenting different clinical and histological characteristics, leading to a challenging scenario in clinical practice. Diffusion-weighted imaging (DWI) has been suggested as an indirect marker of tumor density and cellularity and could be used to monitor therapeutic response. However, its role in pediatric GCTs needs to be clarified. Purpose: Here, we evaluated the features of DWI in pediatric extracranial GCTs in a reference Brazilian institution. Material and methods: We included 43 pediatric patients with primary GCTs treated between 2008 and 2022 in Hospital de Amor de Barretos. The patients' MRI images included T1-weighted without contrast, T2-weighted, DWI and apparent diffusion coefficient (ADC) maps. DWI was evaluated in the section that exhibited the greatest restricted diffusion in the largest hypersignal area of the image. The lowest ADC value was determined to define the region of interest (ROI). We used a small ROI, avoiding necrotic, adipose tissue, noisy or nonenhancing lesion voxels as recommended. ROI determination was established by visual inspection by two radiologists in accordance. We used two values of b (b = 50 mm2/s or b = 800) for ADC values. Results: The highest mean ADC (mADC) value was observed in pure teratomas (1,403.50 ± 161.76 x10-3 mm2/s; mean ± SD) compared to other histologies (yolk sac, mixed teratoma, dysgerminoma and mixed GCT) of GCT (p<0.001). Furthermore, ROC analysis determined a cutoff mADC value of 1,179.00 x 10−3 mm2/s that differentiated pure teratomas from the other GCT histologies with a sensitivity of 95.8% and a specificity of 92.9% (AUC = 0.979; p<0.01). A significant increase in mADC was observed for malignant GCTs in treatment (1,197.00 ± 372.00 mm2/s; p<0.001) compared to that exhibited at the time of diagnosis (780.00 ± 168.00 mm2/s; mean ± SD. Our findings suggest that mADC assessment could be used as a tool to distinguish pure teratomas from malignant CGT histologies at diagnosis. Additionally, we demonstrated reasonable evidence that it could be used as a complementary tool to monitor treatment response in patients with malignant GCT. [ABSTRACT FROM AUTHOR]

An increase in the incidence of arboviral, microbial and parasitic infections, and to disorders related to oxidative stress has encouraged the development of adjuvant therapies based on natural formulations, such as those involving plant extracts. Thus, to expand the repertoire of the available therapeutic options, this study aimed to describe the versatility of Tephrosia toxicaria (Sw.) (Pers., 1807) extracts for the control of arbovirus vectors, as well as their antioxidant, antileishmanial, and antimicrobial potential. Among the aqueous and hydroethanolic extracts obtained, the hydroethanolic extract from roots (RHA) was identified as the most active larvicide extract demonstrating, respectively, the lowest lethal concentration (mg/mL) for 50%, 90% and 99% of Aedes aegypti (L., 1762) and Aedes albopictus (S., 1894) larvae, observed at 24 h (0.33, 0.84 and 1.80; 0.32, 0.70 and 1.32) and 48 h (0.17, 0.51 and 1.22; 0.26, 0.47 and 0.78) post-exposure. Field assays revealed that RHA (0.84 mg/mL) is a potential oviposition deterrent, reducing egg-laying by approximately 90%. RHA (0.1 mg/mL) also exhibited antioxidant activity for the following tests: total antioxidant capacity (286.86 mg AAE/g), iron (87.16%) and copper (25.64%) chelation, and superoxide scavenging (10%). In the cell culture assays, RHA (0.1 mg/mL) promoted regeneration of metabolic activity (92% cell viability) in cells exposed to oxidative stress. Furthermore, RHA displayed weak antileishmanial activity (IC50 = 3.53 mg/mL) against Leishmania amazonensis and not exhibit antimicrobial activity. The extraction favored the concentration of carbohydrates in RHA, in addition to lectins and protease inhibitors, with molecular masses estimated between 10 and 24 kDa. Cytotoxicity and phytotoxicity analyses of RHA suggested its biosecurity. Thus, RHA is a multivalent extract with insecticide and antioxidant properties at low and safe concentrations. However, others studies on its indirect toxic effects are ongoing to ensure the complete safety of RHA. [ABSTRACT FROM AUTHOR]

This study aimed to quantify the influence of clays and partially oxidised cellulose nanofibrils (OCNF) on gelation as well as characterise their physical and chemical interactions. Mixtures of Laponite and montmorillonite clays with OCNF form shear-thinning gels that are more viscous across the entire shear range than OCNF on its own. Viscosity and other rheological properties can be fine-tuned using different types of clay at different concentrations (0.5–2 wt%). Laponite particles are an order of magnitude smaller than those of montmorillonite (radii of 150 Å compared to 2000 Å) and are therefore able to facilitate networking of the cellulose fibrils, resulting in stronger effects on rheological properties including greater viscosity. This work presents a mechanism for modifying rheological properties using renewable and environmentally-friendly nanocellulose and clays which could be used in a variety of industrial products including home and personal care formulations. [ABSTRACT FROM AUTHOR]

This study was designed to evaluate the anti-inflammatory effects of a curcumin treatment on the knee of rats with induced osteoarthritis. Fifteen adult rats were used and divided in three groups: the osteoarthritis group (OAG), control group (CG–without induction of osteoarthritis), and curcumin-treated osteoarthritis group (COAG). Osteoarthritis was induced in the right knee of rats in the OAG and COAG by administering an intra-articular injection of 1 mg of zymosan. Fourteen days after induction, 50 mg/kg curcumin was administered by gavage daily for 60 days to the COAG. After the treatment period, rats from all groups were euthanized. Medial femoral condyles were collected for light microscopy and immunohistochemical staining. The expression of SOX-5, IHH, MMP-8, MMP-13, and collagen 2 (Col2) was analyzed. The COAG exhibited an increase in the number of chondrocytes in the surface and middle layers compared with that of the OAG and CG, respectively. The COAG also showed a decrease in the thicknesses of the middle and deep layers compared with those of the OAG, and an increase in Col2 expression was observed in all articular layers (surface, middle, and deep) in the COAG compared with that in the OAG. SOX-5 expression was increased in the surface and deep layers of the COAG compared with those in the OAG and CG. Based on the results of this study, the curcumin treatment appeared to exert a protective effect on cartilage, as it did not result in an increase in cartilage thickness or in MMP-8 and MMP-13 expression but led to increased IHH, Col2, and SOX-5 expression and the number of chondrocytes. [ABSTRACT FROM AUTHOR]

Limonoids, quinolone alkaloids and chromones have been reported as constituents of Dictyoloma vandellianum Adr. Juss. (Rutaceae). Although those compounds are known for their biological activities, only the anti-inflammatory activity of chromones isolated from the underground parts has been evaluated. There are no studies of the pharmacological properties of the aerial parts of D. vandellianum. The present study was carried out to determine the phytochemical profile and antinociceptive activity of the methanol extract, fractions and isolated compounds of leaves of D. vandellianum. The phytochemical profile was performed by HLPC-DAD-ESIMSn and pure substances obtained were characterized by MS and NMR spectroscopy. The antinociceptive activity was assessed using the formalin assay in mice, and the motor function in the rotarod test. ME and all the fractions obtained from ME produced antinociceptive effects. Among them, the ethyl ether fraction was the most active. Data from HPLC-DAD-ESIMSn showed that the ethyl ether fraction presented 42 compounds. The major compounds isolated from this fraction—gallic acid, methyl gallate and 1,2,6-tri-O-galloyl-β-d-glucopyranose–were tested and produced antinociceptive effects. Gallic acid, methyl gallate and 1,2,6-tri-O-galloyl-β-d-glucopyranose at antinociceptive doses did not affect the motor performance in mice in the rotarod test. This work is the first report of the occurrence of gallotanins in D. vandellianum. In addition, the pharmacological study showed that D. vandellianum leaves present antinociceptive activity, probably induced by gallic acid, methyl gallate and 1,2,6-tri-O-galloyl-β-d-glucopyranose. [ABSTRACT FROM AUTHOR]

This study configures a first report regarding the variability of meat quality of locally adapted Pantaneiro sheep depending on different physiological stages and breeding systems. Pantaneiro sheep are raised in Brazil under a tropical wetland ecosystem denominated Pantanal. Twenty-nine Pantaneiro sheep from different sex and physiological stages were sorted into three groups, simulating three of the most representative ovine meat products commercialized by South American industries: a) non castrated male lambs (n = 11); b) wethers (n = 9); c) cull ewes (n = 9). Animals from each physiological stage were submitted to different breeding systems, resembling farming strategies adopted in several developing countries of South America. The effect of physiological stages on the quality of meat was accessed using 16 variables measured in the longissimus thoracis et lumborum (LM) and the semimembranosus (SM) muscles. The variables were related to brightness, color, physical aspects, soluble and total collagen as well as chemical traits. The physiological stage was defined as a classification variable in order to proceed ANOVA tests and comparison of means (P<0.05). Multivariate analysis was used to identify patterns of similarity and differentiation between samples of different physiological stages (a, b, c). The results revealed that meat quality varies according to different physiological stages, especially between lambs (a) and cull ewes (c). As a consequence, the physiological stage at slaughter should be taken into consideration to cote the quality of meat from indigenous sheep raised in tropical regions. The results contribute towards sensorial evaluation and the characterization of potential food products derived from indigenous sheep bred under tropical climate in developing countries. [ABSTRACT FROM AUTHOR]

This research evaluated a multivariate approach as an alternative tool for the purpose of selection regarding expected progeny differences (EPDs). Data were fitted using a multi-trait model and consisted of growth traits (birth weight and weights at 120, 210, 365 and 450 days of age) and carcass traits (longissimus muscle area (LMA), back-fat thickness (BF), and rump fat thickness (RF)), registered over 21 years in extensive breeding systems of Polled Nellore cattle in Brazil. Multivariate analyses were performed using standardized (zero mean and unit variance) EPDs. The k mean method revealed that the best fit of data occurred using three clusters (k = 3) (P < 0.001). Estimates of genetic correlation among growth and carcass traits and the estimates of heritability were moderate to high, suggesting that a correlated response approach is suitable for practical decision making. Estimates of correlation between selection indices and the multivariate index (LD1) were moderate to high, ranging from 0.48 to 0.97. This reveals that both types of indices give similar results and that the multivariate approach is reliable for the purpose of selection. The alternative tool seems very handy when economic weights are not available or in cases where more rapid identification of the best animals is desired. Interestingly, multivariate analysis allowed forecasting information based on the relationships among breeding values (EPDs). Also, it enabled fine discrimination, rapid data summarization after genetic evaluation, and permitted accounting for maternal ability and the genetic direct potential of the animals. In addition, we recommend the use of longissimus muscle area and subcutaneous fat thickness as selection criteria, to allow estimation of breeding values before the first mating season in order to accelerate the response to individual selection. [ABSTRACT FROM AUTHOR]

Among neglected tropical diseases, leishmaniasis is one of the most important ones, affecting more than 12 million people worldwide. The available treatments are not well tolerated, and present diverse side effects, justifying the search for new therapeutic compounds. In the present study, the activity of ursolic acid (UA) and oleanolic acid (OA) were assayed in experimental cutaneous leishmaniasis (in vitro and in vivo). Promastigote forms of L. amazonensis were incubated with OA and UA for 24h, and effective concentration 50% (EC50) was estimated. Ultraestructural alterations in Leishmania amazonensis promastigotes after UA treatment were evaluated by transmission electron microscopy, and the possible mode of action was assayed through Annexin V and propidium iodide staining, caspase 3/7 activity, DNA fragmentation and transmembrane mitochondrial potential. The UA potential was evaluated in intracellular amastigotes, and its therapeutic potential was evaluated in L. amazonensis infected BALB/c mice. UA eliminated L. amazonensis promastigotes with an EC50 of 6.4 μg/mL, comparable with miltefosine, while OA presented only a marginal effect on promastigote forms at 100 μg/mL. The possible mechanism by which promastigotes were eliminated by UA was programmed cell death, independent of caspase 3/7, but it was highly dependent on mitochondria activity. UA was not toxic for peritoneal macrophages from BALB/c mice, and it was able to eliminate intracellular amastigotes, associated with nitric oxide (NO) production. OA did not eliminate amastigotes nor trigger NO. L. amazonensis infected BALB/c mice submitted to UA treatment presented lesser lesion size and parasitism compared to control. This study showed, for the first time, that UA eliminate promastigote forms through a mechanism associated with programed cell death, and importantly, was effective in vivo. Therefore, UA can be considered an interesting candidate for future tests as a prototype drug for the treatment of cutaneous leishmaniasis. [ABSTRACT FROM AUTHOR]

Telomerase RNAs (TERs) are highly divergent between species, varying in size and sequence composition. Here, we identify a candidate for the telomerase RNA component of Leishmania genus, which includes species that cause leishmaniasis, a neglected tropical disease. Merging a thorough computational screening combined with RNA-seq evidence, we mapped a non-coding RNA gene localized in a syntenic locus on chromosome 25 of five Leishmania species that shares partial synteny with both Trypanosoma brucei TER locus and a putative TER candidate-containing locus of Crithidia fasciculata. Using target-driven molecular biology approaches, we detected a ∼2,100 nt transcript (LeishTER) that contains a 5′ spliced leader (SL) cap, a putative 3′ polyA tail and a predicted C/D box snoRNA domain. LeishTER is expressed at similar levels in the logarithmic and stationary growth phases of promastigote forms. A 5′SL capped LeishTER co-immunoprecipitated and co-localized with the telomerase protein component (TERT) in a cell cycle-dependent manner. Prediction of its secondary structure strongly suggests the existence of a bona fide single-stranded template sequence and a conserved C[U/C]GUCA motif-containing helix II, representing the template boundary element. This study paves the way for further investigations on the biogenesis of parasite TERT ribonucleoproteins (RNPs) and its role in parasite telomere biology. [ABSTRACT FROM AUTHOR]

Açaí (Euterpe oleracea Mart.) has recently emerged as a promising source of natural antioxidants. Despite its claimed pharmacological and nutraceutical value, studies regarding the effects of açaí in vivo are limited. In this study, we use the Caenorhabditis elegans model to evaluate the in vivo antioxidant properties of açaí on an organismal level and to examine its mechanism of action. Supplementation with açaí aqueous extract (AAE) increased both oxidative and osmotic stress resistance independently of any effect on reproduction and development. AAE suppressed bacterial growth, but this antimicrobial property did not influence stress resistance. AAE-increased stress resistance was correlated with reduced ROS production, the prevention of sulfhydryl (SH) level reduction and gcs-1 activation under oxidative stress conditions. Our mechanistic studies indicated that AAE promotes oxidative stress resistance by acting through DAF-16 and the osmotic stress response pathway OSR-1/UNC-43/SEK-1. Finally, AAE increased polyglutamine protein aggregation and decreased proteasome activity. Our findings suggest that natural compounds available in AAE can improve the antioxidant status of a whole organism under certain conditions by direct and indirect mechanisms. [ABSTRACT FROM AUTHOR]

Components of (co)variance and genetic parameters were estimated for adjusted weights at ages 120 (W120), 240 (W240), 365 (W365) and 450 (W450) days of Polled Nellore cattle raised on pasture and born between 1987 and 2010. Analyses were performed using an animal model, considering fixed effects: herd-year-season of birth and calf sex as contemporary groups and the age of cow as a covariate. Gibbs Samplers were used to estimate (co)variance components, genetic parameters and additive genetic effects, which accounted for great proportion of total variation in these traits. High direct heritability estimates for the growth traits were revealed and presented mean 0.43, 0.61, 0.72 and 0.67 for W120, W240, W365 and W450, respectively. Maternal heritabilities were 0.07 and 0.08 for W120 and W240, respectively. Direct additive genetic correlations between the weight at 120, 240, 365 and 450 days old were strong and positive. These estimates ranged from 0.68 to 0.98. Direct-maternal genetic correlations were negative for W120 and W240. The estimates ranged from −0.31 to −0.54. Estimates of maternal heritability ranged from 0.056 to 0.092 for W120 and from 0.064 to 0.096 for W240. This study showed that genetic progress is possible for the growth traits we studied, which is a novel and favorable indicator for an upcoming and promising Polled Zebu breed in Tropical regions. Maternal effects influenced the performance of weight at 120 and 240 days old. These effects should be taken into account in genetic analyses of growth traits by fitting them as a genetic or a permanent environmental effect, or even both. In general, due to a medium-high estimate of environmental (co)variance components, management and feeding conditions for Polled Nellore raised at pasture in tropical regions of Brazil needs improvement and growth performance can be enhanced. [ABSTRACT FROM AUTHOR]

Here, we show the morphological events associated with organelle segregation and their timing in the cell cycle of a reference strain of Leishmania (L.) amazonensis promastigotes, the main causative agent of Tegumentary leishmaniasis in the Americas. We show evidences that during the cell cycle, L. amazonensis promastigotes present two distinct modes of nucleus and kinetoplast segregation, which occur in different temporal order in different proportions of cells. We used DAPI-staining and EdU-labeling to monitor the segregation of DNA-containing organelles and DNA replication in wild-type parasites. The emergence of a new flagellum was observed using a specific monoclonal antibody. The results show that L. amazonensis cell cycle division is peculiar, with 65% of the dividing cells duplicating the kinetoplast before the nucleus, and the remaining 35% doing the opposite or duplicating both organelles concomitantly. In both cases, the new flagellum appeared during S to G2 phase in 1N1K cells and thus before the segregation of both DNA-containing organelles; however, we could not determine the exact timing of flagellar synthesis. Most of these results were confirmed by the synchronization of parasites using hydroxyurea. Altogether, our data show that during the cell cycle of L. amazonensis promastigotes, similarly to L. donovani, the segregation of nucleus and kinetoplast do not follow a specific order, especially when compared to other trypanosomatids, reinforcing the idea that this characteristic seems to be species-specific and may represent differences in cellular biology among members of the Leishmania genus. [ABSTRACT FROM AUTHOR]

Limonoids, quinolone alkaloids and chromones have been reported as constituents of Dictyoloma vandellianum Adr. Juss. (Rutaceae). Although those compounds are known for their biological activities, only the anti-inflammatory activity of chromones isolated from the underground parts has been evaluated. There are no studies of the pharmacological properties of the aerial parts of D. vandellianum. The present study was carried out to determine the phytochemical profile and antinociceptive activity of the methanol extract, fractions and isolated compounds of leaves of D. vandellianum. The phytochemical profile was performed by HLPC-DAD-ESIMSn and pure substances obtained were characterized by MS and NMR spectroscopy. The antinociceptive activity was assessed using the formalin assay in mice, and the motor function in the rotarod test. ME and all the fractions obtained from ME produced antinociceptive effects. Among them, the ethyl ether fraction was the most active. Data from HPLC-DAD-ESIMSn showed that the ethyl ether fraction presented 42 compounds. The major compounds isolated from this fraction-gallic acid, methyl gallate and 1,2,6-tri-O-galloyl-β-d-glucopyranose-were tested and produced antinociceptive effects. Gallic acid, methyl gallate and 1,2,6-tri-O-galloyl-β-d-glucopyranose at antinociceptive doses did not affect the motor performance in mice in the rotarod test. This work is the first report of the occurrence of gallotanins in D. vandellianum. In addition, the pharmacological study showed that D. vandellianum leaves present antinociceptive activity, probably induced by gallic acid, methyl gallate and 1,2,6-tri-O-galloyl-β-d-glucopyranose., Competing Interests: The authors have declared that no competing interests exist.

Açaí (Euterpe oleracea Mart.) has recently emerged as a promising source of natural antioxidants. Despite its claimed pharmacological and nutraceutical value, studies regarding the effects of açaí in vivo are limited. In this study, we use the Caenorhabditis elegans model to evaluate the in vivo antioxidant properties of açaí on an organismal level and to examine its mechanism of action. Supplementation with açaí aqueous extract (AAE) increased both oxidative and osmotic stress resistance independently of any effect on reproduction and development. AAE suppressed bacterial growth, but this antimicrobial property did not influence stress resistance. AAE-increased stress resistance was correlated with reduced ROS production, the prevention of sulfhydryl (SH) level reduction and gcs-1 activation under oxidative stress conditions. Our mechanistic studies indicated that AAE promotes oxidative stress resistance by acting through DAF-16 and the osmotic stress response pathway OSR-1/UNC-43/SEK-1. Finally, AAE increased polyglutamine protein aggregation and decreased proteasome activity. Our findings suggest that natural compounds available in AAE can improve the antioxidant status of a whole organism under certain conditions by direct and indirect mechanisms.

Here, we show the morphological events associated with organelle segregation and their timing in the cell cycle of a reference strain of Leishmania (L.) amazonensis promastigotes, the main causative agent of Tegumentary leishmaniasis in the Americas. We show evidences that during the cell cycle, L. amazonensis promastigotes present two distinct modes of nucleus and kinetoplast segregation, which occur in different temporal order in different proportions of cells. We used DAPI-staining and EdU-labeling to monitor the segregation of DNA-containing organelles and DNA replication in wild-type parasites. The emergence of a new flagellum was observed using a specific monoclonal antibody. The results show that L. amazonensis cell cycle division is peculiar, with 65% of the dividing cells duplicating the kinetoplast before the nucleus, and the remaining 35% doing the opposite or duplicating both organelles concomitantly. In both cases, the new flagellum appeared during S to G2 phase in 1N1K cells and thus before the segregation of both DNA-containing organelles; however, we could not determine the exact timing of flagellar synthesis. Most of these results were confirmed by the synchronization of parasites using hydroxyurea. Altogether, our data show that during the cell cycle of L. amazonensis promastigotes, similarly to L. donovani, the segregation of nucleus and kinetoplast do not follow a specific order, especially when compared to other trypanosomatids, reinforcing the idea that this characteristic seems to be species-specific and may represent differences in cellular biology among members of the Leishmania genus.