MKRN3 mutations represent the most common genetic cause of central precocious puberty (CPP) but associations between genotype and clinical features have not been extensively explored. This systematic review and meta-analysis investigated genotype-phenotype associations and prevalence of MKRN3 mutations in CPP. The search was conducted in seven electronic databases (Cochrane, EMBASE, LILACS, LIVIVO, PubMed, Scopus, and Web of Science) for articles published until 4 September 2018. Studies evaluating MKRN3 mutations in patients with CPP were considered eligible. A total of 22 studies, studying 880 subjects with CPP, fulfilled the inclusion criteria. Eighty-nine subjects (76 girls) were identified as harboring MKRN3 mutations. Girls, compared with boys, exhibited earlier age at pubertal onset (median, 6.0 years; range, 3.0 to 7.0 vs 8.5 years; range, 5.9 to 9.0; P < 0.001), and higher basal FSH levels (median, 4.3 IU/L; range, 0.7 to 13.94 IU/L vs 2.45 IU/L; range, 0.8 to 13.70 IU/L; P = 0.003), and bone age advancement ( Δ BA; median, 2.3 years; range, −0.9 to 5.2 vs 1.2 years; range, 0.0 to 2.3; P = 0.01). Additional dysmorphisms were uncommon. A total of 14 studies evaluating 857 patients were included for quantitative analysis, with a pooled overall mutation prevalence of 9.0% (95% CI, 0.04 to 0.15). Subgroup analysis showed that prevalence estimates were higher in males, familial cases, and in non-Asian countries. In conclusion, MKRN3 mutations are associated with nonsyndromic CPP and manifest in a sex-dimorphic manner, with girls being affected earlier. They represent a common cause of CPP in western countries, especially in boys and familial cases.

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Prostate cancer remains a health problem for men. Targeting androgen (AR) and estrogen (ER) receptors improves the outcomes of the disease, and many medicinal plants exert their effects by modulating these pathways. Therefore, a systematic review was conducted to identify medicinal plants and their natural compounds that may modulate the AR and/or ER pathways in cell and animal models. A search was conducted across EMBASE, LILACS, PubMed, Scopus, and Web of Science, with grey literature from Google SCHOLAR and ProQuest. Two authors independently selected eligible studies based on their titles and abstracts, and a third author resolved conflicts. Then, data from the full text of eligible studies were extracted and synthesized.In total, 75 studies were included. Results showed the effects of several different medicinal plants and natural compounds in reduction of AR and/or ER transcription and translation and AR secondary effects: cell growth reduction, induction of apoptosis, and cell cycle arrest. In animal models, tumor size reduction, increase in apoptosis, and downregulation of AR expression in tumors were also observed. No single phytochemical group concentrating molecules with anti-AR and/or ER activity was identified. Nevertheless, several phytochemical compounds showed potential for future clinical studies in the management of the disease.

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Hippeastrum stapfianum (Kraenzl.) R.S.Oliveira & Dutilh (Amaryllidaceae) is an endemic plant species from the Brazilian savannah with biological and pharmacological potential. This study evaluated the effects of ethanol extract from H. stapfianum leaves on acetylcholinesterase enzyme activity and the action on nuclear receptors PPAR-α and PPAR-γ. A gene reporter assay was performed to assess the PPAR agonist or antagonist activity with a non-toxic dose of H. stapfianum ethanol extract. The antioxidant capacity was investigated using DPPH• scavenging and fosfomolybdenium reduction assays. The identification of H. stapfianum‘s chemical composition was performed by gas chromatography–mass spectrometry (GC-MS) and HPLC. The ethanol extract of H. stapfianum activated PPAR-α and PPAR-γ selectively, inhibited the acetylcholinesterase enzyme, and presented antioxidant activity in an in vitro assay. The major compounds identified were lycorine, 7-demethoxy-9-O-methylhostasine, and rutin. Therefore, H. stapfianum is a potential source of drugs for Alzheimer’s disease due to its ability to activate PPAR receptors, acetylcholinesterase inhibition activity, and antioxidant attributes.

A Deus e nossa senhora do Carmo que me deram força para sempre seguir em frente.À minha mãe Maize e ao meu pai Antônio pelo amor, apoio, dedicação e suporte para meus estudos. Às minhas irmãs Camila e Carina pela ajuda e companheirismo. À minha vó, meus tios e tias, primos e primas, muito obrigada pela força, apoio e amizade.Aos meus orientadores, professor Luiz e a professora Adriana, meus amigos, meus exemplos. Muito obrigada pela oportunidade, por tudo que me foi ensinado durante o mestrado e pela confiança.Aos colegas e amigos do FarMol em especial: Bia, Olivia, Carol Martins, Fernanda, Nadyellem, Yasmim, Carol Lourenço, Flora, Mariella, Erica, Sidney, Sarah e a todos os professores do FarMol pela ajuda e amizade.A todos do Laboratório de Histopatologia Bucal da Universidade de Brasília em especial à professora Eliete Neves e à professora Ana Carolina por conceder o espaço para realização dos experimentos, pelo apoio e ajuda. À Dani, Silvinha e Gabriel meu sincero agradecimento por toda ajuda e pela amizade.Ao Laboratório de Biologia Celular e Molecular de Universidade de Campinas, Professor Ricardo Coletta e Fábio Haach Téo pela ajuda na leitura dos experimentos do ciclo celular.Ao CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico) pelo auxílio bolsa e verba para realização da pesquisa. 7"Todo caminho da gente é resvaloso. Mas também, cair não prejudica demaisa gente levanta, a gente sobe, a gente volta!... O correr da vida embrulha tudo, a vida é assim: esquenta, esfria, aperta e daí afrouxa, sossega e depois desinquieta. O que ela quer da gente é CORAGEM." João Guimarães Rosa