The bioprospecting potential of Clusia fluminensis Planch. & Triana: a scoping review.

Many biological activities are described for the Clusiaceae family. Clusia fluminensis, a species from Brazilian flora, is mainly employed for ornamental purposes. This review aimed to depict the current knowledge of C. fluminensis from a bioprospecting standpoint. "Clusia fluminensis" search term was applied in Scopus, Web of Science, PubMed and Bireme databases according to PRISMA-ScR statement. Selected papers on Phytochemistry or Bioactivity followed hand searching procedures. Bioactivity preclinical studies considered in vitro or in vivo biological systems, treated with plant extracts or isolated compounds. The outcomes were compared with standard or no treatment control groups. Critical appraisal of individual trials considered completeness in the research fields. Our results showed that 81% of the selected papers presented high level of completeness, 69% revealed phytochemical parameters and 31% biological applications of plant extracts and isolated compounds. Polyisoprenylated benzophenones, terpenoids, sterols and phenolic compounds were identified. Antiviral, insecticidal and snake antivenom activities were reported. In conclusion, the phytochemical data reinforce the reported activities. Potential applications in personal care, nutritional supplementation and pharmaceutical, food, chemical or textile industries were also identified. Toxicological and phytochemical complementary studies may be required.

Molecular biology techniques for loss of heterozygosity detection: the glioma example / Técnicas de biologia molecular para avaliação da perda de heterozigosidade: o exemplo em glioma

ABSTRACT In recent years, many oncology institutions have implemented the use of molecular approaches to assess and manage cancer patients. One commonly observed type of genetic alteration in cancer is the loss of heterozygosity (LOH). In the clinical setting, this molecular genetic marker is an important tool for disease prognosis, diagnosis and treatment. For example, the loss of 1p/19q is a classical molecular marker for oligodendroglioma assessment. In addition, this marker is associated with a favorable prognosis and chemosensitivity in oligodendroglial tumors. Interpretation of the clinical significance of molecular markers requires that health professionals and biomedical scientists understand the basic theoretical fundamentals of molecular diagnostic techniques. Although there are different methodologies to assess LOH, including high-performance techniques, this review aims to describe the polymerase chain reaction (PCR)-based LOH assays and fluorescence in situ hybridization (FISH), which are the molecular techniques most used for evaluation of 1p/19q status in pathology laboratories.

RESUMO Nos últimos anos, instituições de oncologia têm implementado o uso de abordagens moleculares para avaliar e conduzir pacientes com câncer. O tipo mais comum de alteração encontrada no câncer é a perda de heterozigosidade (LOH). Na clínica, esse marcador molecular pode ter importância para o prognóstico, o diagnóstico e/ou na decisão do tratamento. Por exemplo, a perda de 1p/19q é um marcador molecular clássico para a avaliação do oligodendroglioma. Além disso, esse marcador está associado ao prognóstico favorável e à quimiossensibilidade em tumores oligodendrogliais. A interpretação do significado clínico dos marcadores moleculares exige que os profissionais da área da saúde entendam os fundamentos básicos teóricos das técnicas de diagnóstico molecular. Embora existam diferentes metodologias para avaliar a LOH, inclusive técnicas de alta performance, esta revisão tem o objetivo de descrever o ensaio de LOH com base na reação da cadeia da polimerase (PCR) e a hibridização in situ fluorescente (FISH), que são as técnicas moleculares mais usadas para avaliação do status 1p/19q em laboratórios de patologia.

Triterpene esters and biological activities from edible fruits of Manilkara subsericea (Mart.) Dubard, Sapotaceae.

Manilkara subsericea (Mart.) Dubard (Sapotaceae) is popularly known in Brazil as "guracica." Studies with Manilkara spp indicated the presence of triterpenes, saponins, and flavonoids. Several activities have been attributed to Manilkara spp such as antimicrobial, antiparasitic and antitumoral, which indicates the great biological potential of this genus. In all, 87.19% of the hexanic extract from fruits relative composition were evaluated, in which 72.81% were beta- and alpha-amyrin esters, suggesting that they may be chemical markers for M. subsericea. Hexadecanoic acid, hexadecanoic acid ethyl ester, (E)-9-octadecenoic acid ethyl ester, and octadecanoic acid ethyl ester were also identified. Ethanolic crude extracts from leaves, stems, and hexanic extract from fruits exhibited antimicrobial activity against Staphylococcus aureus ATCC25923. These extracts had high IC50 values against Vero cells, demonstrating weak cytotoxicity. This is the first time, to our knowledge, that beta- and alpha-amyrin caproates and caprylates are described for Manilkara subsericea.

Antiproliferative activity of Eremanthus crotonoides extracts and centratherin demonstrated in brain tumor cell lines

The genus Eremanthus is recognized by the predominance of sesquiterpene lactones from the furanoheliangolide type, a class of substances extensively tested against cancer cell lines. Thus, the species E. crotonoides (DC.) Sch. Bip., Asteraceae, obtained on "restinga" vegetation was evaluated against U251 and U87-MG glioma cell lines using the MTT colorimetric assay. Dichloromethane fraction was cytotoxic to both glioblastoma multiforme cell lines. We then conducted UPLC-PDA-ESI-MS/MS analysis of the dichloromethane fraction, which allowed the identification of the sesquiterpene lactones centratherin and goyazensolide. The isolation of centratherin was performed using chromatographic techniques and the identification of this substance was confirmed according to NMR data. Cytotoxic activity of centratherin alone was also evaluated against both U251 and U87-MG cells, which showed IC50 values comparable with those obtained for the commercial anticancer drug doxorubicin. All the tested samples showed cytotoxic activity against glioblastoma multiforme cells which suggests that E. crotonoides extracts may be important sources of antiproliferative substances and that the centratherin may serve as prototype for developing new antiglioblastoma drugs.

The anticancer drug perillyl alcohol is a Na/K-ATPase inhibitor.

The monoterpene perillyl alcohol (POH) is a drug used in the treatment of several malignant tumors, including gliomas. The present study defines a POH inhibitory effect on Na/K-ATPase activity from kidney and brain guinea pig extracts and from a human glioblastoma cell line. This inhibition showed a high degree of selectivity toward the kidney enzyme expressing, as do glioblastoma cells, the α(1) subunit. Kinetic studies with purified enzymes showed a noncompetitive POH inhibition profile to Na(+) and K(+) and an uncompetitive inhibition towards ATP. Furthermore, potassium activated p-nitrophenylphosfatase activity of these purified preparations was not inhibited by POH, suggesting that this drug, differently from the classical inhibitor ouabain, acted in the initial phase of the enzyme's catalytic cycle. We suggest that POH antitumor action could be linked to its Na/K-ATPase binding properties.

TP53 mutations in breast cancer tumors of patients from Rio de Janeiro, Brazil: association with risk factors and tumor characteristics.

Somatic mutations in the TP53 gene are the most frequently observed genetic alterations in human malignancies, including breast cancer, which is one of the leading causes of death among women in Brazil. In our study, we determined the frequency and the pattern of TP53 mutations in malignant breast tumors from 120 patients living in Rio de Janeiro, Brazil. TP53 mutations were found in 20% of the tumors, which contained a diversity of mutation types: missense (62.5%), nonsense (8.3%), silent (4.2%), intronic (12.5%), insertion (4.2%) and deletion (8.3%). Of a total of 15 missense mutations, 4 were observed at Arg248 and 2 at Cys242, which are directly involved in DNA binding and in zinc binding, respectively. A subgroup of 51 patients was analyzed with respect to the relation between the presence of TP53 mutations and classical risk factors and with tumor and patient characteristics. For this analysis, we used logistic regression and, in order to obtain more precise confidence intervals, they were recalculated using a bootstrap resampling technique. Our results demonstrate that these mutations are not statistically associated with the risk factors or the patients' characteristics. However, the presence of TP53 mutations is strongly associated with the aggressiveness of the tumors, measured by Elston classification (OR = 11.97 and 95% CI of 2.24-307.05). This finding is in agreement with previous studies, which report the presence of TP53 mutations in tumors with poor prognosis. This correlation between tumor aggressiveness and TP53 mutations could be a crucial variable for the treatment and prognosis of breast cancer.

Frequencies of GSTM1, GSTT1, and GSTP1 polymorphisms in a Brazilian population

The glutathione S-transferase (GST) family of enzymes has a vital role in phase II of biotransformation of environmental carcinogens, pollutants, drugs and other xenobiotics. GSTs are polymorphic, with the type and frequency of polymorphism being ethnic dependent. Polymorphisms in GST genes have been shown to be associated with susceptibility to disease and disease outcome. We determined the frequencies of GSTM1, GSTT1 and GSTP1 polymorphisms in 591 volunteers who had been residents of Rio de Janeiro for at least six months. Blood was collected and DNA extracted by proteinase K/SDS digestion. Information about social habits and health problems was also recorded. GSTM1 and GSTT1 polymorphisms were analyzed by a PCR-Multiplex procedure, whereas GSTP1 polymorphism was analyzed by PCR-RFLP. We found that 42.1% (48.9% of whites and 34.2% of non-whites) of the individuals had the GSTM1 null genotype, whereas 25.4% (25.1% of whites and 25.7% of non-whites) had the GSTT1 null genotype. The genotypic distribution of GSTP1 was 49.7% I/I, 38.1% I/V, and 12.2% V/V, whereas the allelic frequencies were 0.69 for the Ile allele, and 0.31 for the Val allele. The frequencies of GST polymorphisms in this Brazilian population were found to be different from those observed in other populations, particularly of other South American countries.

Frequencies of GSTM1, GSTT1, and GSTP1 polymorphisms in a Brazilian population.

The glutathione S-transferase (GST) family of enzymes has a vital role in phase II of biotransformation of environmental carcinogens, pollutants, drugs and other xenobiotics. GSTs are polymorphic, with the type and frequency of polymorphism being ethnic dependent. Polymorphisms in GST genes have been shown to be associated with susceptibility to disease and disease outcome. We determined the frequencies of GSTM1, GSTT1 and GSTP1 polymorphisms in 591 volunteers who had been residents of Rio de Janeiro for at least six months. Blood was collected and DNA extracted by proteinase K/SDS digestion. Information about social habits and health problems was also recorded. GSTM1 and GSTT1 polymorphisms were analyzed by a PCR-Multiplex procedure, whereas GSTP1 polymorphism was analyzed by PCR-RFLP. We found that 42.1% (48.9% of whites and 34.2% of non-whites) of the individuals had the GSTM1 null genotype, whereas 25.4% (25.1% of whites and 25.7% of non-whites) had the GSTT1 null genotype. The genotypic distribution of GSTP1 was 49.7% I/I, 38.1% I/V, and 12.2% V/V, whereas the allelic frequencies were 0.69 for the Ile allele, and 0.31 for the Val allele. The frequencies of GST polymorphisms in this Brazilian population were found to be different from those observed in other populations, particularly of other South American countries.