DOPA decarboxylase (DDC; aromatic‐l‐amino acid decarboxylase; EC 4.1.1.28) is absent in retinas from 6‐day‐old chicken embryos (E6) but is expressed in retina of E8 embryos, in the presumptive outer ...plexiform layer. Thereafter, DDC appears in cell bodies of presumptive amacrine cells. The dopamine (DA) content of E9/10 and E15/16 retinas, pre‐incubated with l‐DOPA for 1 h, increased 250‐ and 600‐fold, respectively, showing that DDC is active since early in development. Intercellular communication, measured by endogenous cyclic AMP accumulation, was observed when retinas from E9/10 to E15/16 were pre‐incubated for 1 h with 1 mm l‐DOPA, washed and followed by incubation in the presence of 0.5 mm 3‐isobutyl‐1‐methylxanthine, a phosphodiesterase inhibitor. Cyclic AMP accumulation was prevented when pre‐incubation with l‐DOPA was carried out in the presence of carbidopa. Moreover, the accumulation of cyclic AMP was inhibited by SCH 23390 (2 µm). The incubation of retinas in medium previously conditioned by retina‐pigmented epithelium (RPE) also increased its cyclic AMP content with the characteristics described for l‐DOPA. Our results show that dopaminergic communication takes place in the embryonic retina, before tyrosine hydroxylase expression, provided l‐DOPA is supplied to the tissue. It also shows that RPE is a potential source of l‐DOPA early in development.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Somatic mutations in the promoter region of telomerase reverse transcriptase (TERT) gene, mainly at positions c.-124 and c.-146 bp, are frequent in several human cancers; yet its presence in ...gastrointestinal stromal tumor (GIST) has not been reported to date. Herein, we searched for the presence and clinicopathological association of TERT promoter mutations in genomic DNA from 130 bona fide GISTs. We found TERT promoter mutations in 3.8% (5/130) of GISTs. The c.-124C>T mutation was the most common event, present in 2.3% (3/130), and the c.-146C>T mutation in 1.5% (2/130) of GISTs. No significant association was observed between TERT promoter mutation and patient's clinicopathological features. The present study establishes the low frequency (4%) of TERT promoter mutations in GISTs. Further studies are required to confirm our findings and to elucidate the hypothetical biological and clinical impact of TERT promoter mutation in GIST pathogenesis.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Treatment strategies for oral squamous cell carcinoma (OSCC) vary, depending on the stage of diagnosis. Surgery and radiotherapy are options for localized lesions for stage I patients, whereas ...chemotherapy is the main treatment for metastatic OSCC. However, aggressive tumors can relapse, frequently causing death. In an attempt to address this, novel treatment protocols using drugs that alter the epigenetic profile have emerged as an alternative to control tumor growth and metastasis. Therefore, the objective in this study was to investigate the effect of the demethylating drug 5-aza-CdR in SCC9 OSCC cells.
SCC9 cells were treated with 5-Aza-CdR at concentrations of 0.3μM and 2μM for 24hours and 48hours. DNA methylation of the MGMT, BRCA1, APC, c-MYC, and hTERT genes were investigated by using the methylation-specific high-resolution melting technique. Real time–polymerase chain reaction and quantitative polymerase chain reaction were performed to analyze gene expression.
5-Aza-CdR promoted demethylation of MGMT and modified the transcription of all analyzed genes. Curiously, 5-aza-CdR at the concentration of 0.3μM was more efficient than 2μM in SCC9 cells.
We observed that 5-aza-CdR led to MGMT demethylation, upregulated the transcription of 3 important tumor suppressor genes, and promoted the downregulation of c-Myc.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Rheumatoid arthritis (RA) composite disease activity indices have become handy tools in daily clinical practice and crucial in defining remission or low disease activity, the main target of the RA ...treatment. However, there is no definition of the best index to assess disease activity in clinical practice. To compare the residual activity among the indices with the ACR/EULAR remission criteria (Boolean method) to identify the most feasible for assessing remission in daily practice, also considering correlation and concordance, sensibility, and specificity. We selected 1116 patients with established RA from the real-life rheumatoid arthritis study database-REAL. The composite disease activity indices-DAS28-ESR, DAS28-CRP, SDAI, and CDAI-and their components were compared to the Boolean method to identify residual activity using binomial regression. The indices were analyzed for correlation and agreement using the Spearman index and weighted kappa. The chi-square test evaluated sensibility and specificity for remission based on the Boolean method. DAS28-CRP overestimated remission and confirmed higher residual activity than SDAI and CDAI. The indices showed good correlation and agreement, with a better relationship between SDAI and CDAI (k:0,88). CDAI and SDAI showed higher sensitivity and specificity for remission based on the Boolean method. CDAI was performed in 99% of patients, while DAS28 and SDAI were completed in approximately 85%. Although all composite indices of activity can be used in clinical practice and showed good agreement, CDAI and SDAI have better performance in evaluating remission based on the Boolean method, showing less residual activity and higher sensibility and specificity. In addition, CDAI seems to be more feasible for disease activity evaluation in daily clinical practice, especially in developing countries.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Context
Loss-of-function mutations of makorin RING finger protein 3 (MKRN3) are the most common monogenic cause of familial central precocious puberty (CPP).
Objective
To describe the ...clinical and hormonal features of a large cohort of patients with CPP due to MKRN3 mutations and compare the characteristics of different types of genetic defects.
Methods
Multiethnic cohort of 716 patients with familial or idiopathic CPP screened for MKRN3 mutations using Sanger sequencing. A group of 156 Brazilian girls with idiopathic CPP (ICPP) was used as control group.
Results
Seventy-one patients (45 girls and 26 boys from 36 families) had 18 different loss-of-function MKRN3 mutations. Eight mutations were classified as severe (70% of patients). Among the 71 patients, first pubertal signs occurred at 6.2 ± 1.2 years in girls and 7.1 ± 1.5 years in boys. Girls with MKRN3 mutations had a shorter delay between puberty onset and first evaluation and higher follicle-stimulating hormone levels than ICPP. Patients with severe MKRN3 mutations had a greater bone age advancement than patients with missense mutations (2.3 ± 1.6 vs 1.6 ± 1.4 years, P = .048), and had higher basal luteinizing hormone levels (2.2 ± 1.8 vs 1.1 ± 1.1 UI/L, P = .018) at the time of presentation. Computational protein modeling revealed that 60% of the missense mutations were predicted to cause protein destabilization.
Conclusion
Inherited premature activation of the reproductive axis caused by loss-of-function mutations of MKRN3 is clinically indistinct from ICPP. However, the type of genetic defect may affect bone age maturation and gonadotropin levels.
The state of Goiás, in central Brazil, is covered mainly by the Cerrado domain, with the Alto Paraná Atlantic Forest occupying its central-southern portion. Goiás is one of the 20 Brazilian ...federative units without a mammal checklist. In this study, we provide the first checklist of mammals from Goiás state. We recorded mammal species based primarily on the analysis of specimens housed in scientific collections as well as on literature with associated voucher material. We listed 191 mammalian species belonging to 125 genera, 31 families and 10 orders, which represents 25.2% of the mammal species occurring in Brazil. The most speciose orders were Chiroptera (90 spp.), followed by Rodentia (43 spp.), Carnivora (19 spp.) and Didelphimorphia (17 spp.). The following orders accounted for a smaller portion of the state diversity: Cetartiodactyla (7 spp.), Cingulata (7 spp.), Primates (4 spp.), Pilosa (2 spp.), Lagomorpha (1 sp.), and Perissodactyla (1 sp.). A total of 28 species (14.7%), mainly represented by medium and large-sized mammals, are nationally threatened while 12 (6.3%) are globally threatened. Our results indicate great portions of the state lacking a proper survey of mammals, especially the northwestern portion. We discuss species richness, distribution and conservation status of the mammals of Goiás state in national and regional scenarios. We highlight the need for mammal inventories based on complementary survey techniques with the collection of vouchers in order to provide karyologic, molecular, morphologic, parasitologic, and ecological data. These informations are the basis for integrative studies that lead to the understanding of current mammalian richness and diversity. Indeed, knowledge on species richness distribution in the state will guide conservation strategies, especially in areas undergoing habitat loss and fragmentation, such as the central-southern portion of Goiás.
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Hyperuricemia is the main cause of gout, an inflammation induced by uric acid deposition in joints. Drugs available present side effects, so there is a need for new treatment ...alternatives. Lychnophora species are used in folk medicine to treat inflammation, rheumatism and muscle pain. Goyazensolide (10mg/kg), eremantholide C (25mg/kg) and lychnopholide (25mg/kg), sesquiterpene lactones isolated from Lychnophora species were previously studied and showed anti-hyperuricemic effects in mice. However, the mechanisms of this effect were not elucidated. The methodology of this study consisted in treatment of hyperuricemic-induced rats, and comparison between control groups, clinically used anti-hyperuricemic drugs and sesquiterpene lactones. Urine and blood were collected for uric acid quantification. Xanthine oxidase inhibition was measured in liver homogenates. Results showed that all evaluated sesquiterpene lactones presented anti-hyperuricemic activity at the doses of 5 and 10mg/kg and can act through one or both mechanisms, depending on the dose administrated. Goyazensolide and lychnopholide at dose of 5mg/kg showed important uricosuric effect. Goyazensolide and lychnopholide at dose of 10mg/kg, and eremantholide C (5 and 10mg/kg) presented notable inhibition of hepatic xanthine oxidase activity and uricosuric effect. Thus, these sesquiterpene lactones are promising hypouricemic agent to treat hyperuricemia and gout.
The cellulose nanocrystals, also known as nanowhiskers, are particles extracted from crystalline regions of cellulose in which one of its dimensions is on the nanometric scale. They have the ...following advantages: low density, renewable character, good mechanical properties, availability, biodegradability and can be obtained from various vegetable fibers, whom originated from biomass residues, through different methods. For example, the acid hydrolysis in controlled conditions destroys the amorphous regions between the cellulose microfibrils. Brazil has a high lignocellulosic biomass availability deriving from waste produced in different industrial sectors. This, combined with the necessity to employ renewable resources for production of new materials, inspires a great opportunity for technological advancements, adding value to agribusiness products. The fibers of a kind of palm (Elaeis guineensis) and of bromelia (Bromeliaceae) are highlighted in this work as a source for obtaining cellulose nanowhiskers.This study aimed to obtain and characterize through TG, DSC, FTIR, XRD and TEM two different cellulose nanowhiskers and from two studied fibers, as well as to compare them as raw materials for future use as reinforcement in polymers composites. From the results of the TEM, it could be inferred that the acid hydrolysis allowed the attainment of nanowhiskers with a needle format. Based on the results of XRD and TG, the bromelia fibers had higher thermal stability and higher crystallinity index when compared to the palm fibers.
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